Olfactory dysfunction in chronic stroke patients.

BACKGROUND: The aim of the study was to investigate odor identification performance in patients one year after hospital admittance due to stroke. Predictors for olfactory dysfunction were investigated as well as self-reported olfactory function and pleasantness of olfactory items. METHODS: A 1-year prospective study was performed. Stroke location, classification and comorbidities were registered at hospital admission. One year after admission, olfactory function was assessed using standardized olfactory methods (screening for loss of detection sensitivity and an odor identification test). A group of matched controls was derived from a population-based study to compare odor identification performance between groups. Patients were asked for their personal judgment regarding their olfactory function and pleasantness of odorous items. In addition, global cognitive function and symptoms of depression were assessed. RESULTS: A total of 78 patients were enrolled (46 males, 32 females; mean age 68 years) of which 28.2% exhibited reduced olfactory function (hyposmia) and 15.4% exhibited loss of olfactory function (10.3% functional anosmia, 5.1% complete anosmia). Patients showed significantly lower olfactory performance compared to age- and sex-mated matched controls. Predictors of impaired olfactory function were age and NIHSS score. Self-reports indicated no significant differences between patients with normal olfactory function and those with reduced function. Yet, patients having an olfactory dysfunction rated odorous items as significantly less pleasant compared to patients without dysfunction. CONCLUSIONS: Olfactory dysfunction seems to occur frequently after stoke even one year after initial admission. The deficits seem to relate to hyposmia and functional anosmia, and less to a complete loss of smell sensitivity.

Heredity of nasal polyps.

BACKGROUND: Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. METHODOLOGY: Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. RESULTS: During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. CONCLUSION: This study strongly indicates that heredity is a factor of importance for development of nasal polyps.

Normative data for the chemical sensitivity scale for sensory hyperreactivity: the Västerbotten environmental health study.

OBJECTIVES: The chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) is used to quantify affective reactions to and behavioral disruptions by odorous/pungent substances in the environment and has documented good metric properties. However, normative data have not been available. The main objective of the present study was therefore to establish normative data for reference by means of a large-scale population-based study. MATERIALS AND METHODS: From a random sample of 8,520 reachable inhabitants in the county of Västerbotten in Sweden, aged 18-79 years, stratified for age and gender, 3,406 individuals agreed to participate. RESULTS: The results show fairly high internal consistency (Cronbach's α = 0.78-0.83) of the CSS-SHR and that it generates scores with approximately normal distributions (skewness: 0.045-0.454; kurtosis: -0.314 to 0.230), irrespective of age group and gender. Mean scores, standard deviations, confidence intervals, and proportions of individuals who met the diagnostic cutoff score for the CSS-SHR were obtained for reference of normality. CONCLUSIONS: CSS-SHR can be recommended for quantification of affective reactions to and behavioral disruptions by odorous/pungent environmental substances, and with the advantage of comparing scores with normality.

Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

Dyspnea from exercise in cold air is not always asthma.

In the absence of other explanations, exercise-induced dyspnea is often labeled as a manifestation of asthma. The aim of this study was to use exercise provocation in cold air among patients with exercise-induced dyspnea, but without any bronchoconstriction, in order to study induced symptoms and different physiological parameters and to measure the possible influence of exercise in cold air on capsaicin cough sensitivity. Eleven patients with exercise-induced dyspnea but no asthma, along with 11 healthy controls, performed a capsaicin inhalation provocation on two occasions. One of these provocations was preceded by an exercise provocation in a cold chamber. Number of coughs, airway symptoms, spirometry, respiratory rate, pulse rate, end-tidal CO(2), and PSaO(2) were registered. During exercise, the patients coughed more than the controls and also had more airway symptoms. After exercise provocation, spirometry values remained unchanged, but capsaicin cough sensitivity was increased and end-tidal CO(2) decreased among the patients, both in comparison to the controls and in comparison to the patients themselves prior to exercise. Exercise-induced dyspnea may be associated with hypocapnia from hyperventilation and increased capsaicin cough sensitivity. The diagnosis of exercise-induced asthma should be questioned when the patient has no signs of bronchoconstriction.

Prevalence and risk factors for chemical sensitivity and sensory hyperreactivity in teenagers.

The prevalence of chemical sensitivity (CS) and sensory hyperreactivity (SHR) was assessed in a teenage population. Among a random sample of 401 teenagers, 326 (81.3%) answered questionnaires assessing sensitivity to chemicals and noise, anxiety and depression. A subgroup of 85 teenagers conducted a capsaicin inhalation test. The estimated prevalence was 15.6% for general self-reported CS, 3.7% for CS with affective and behavioral consequences, about 1% for SHR. Sensitivity variables were positively intercorrelated. Risk factors for general CS were noise sensitivity (OR: 2.1), probable anxiety (OR: 2.5) and female sex (OR: 2.0). CS problems seem to be present also in teenagers, although less so than in adults. Furthermore, CS seems to be related to other environmental sensitivities.

Voice change in seasonal allergic rhinitis.

Voice problems are seldom reported in pollen allergy, although the allergic reaction involves the entire airways. The objective of this study was to investigate voice dysfunction during the pollen season in patients with allergic rhinitis. Thirty patients with verified birch pollen allergy and 30 controls were investigated twice, during the pollen season and outside the pollen season. Both times they scored respiratory and voice symptoms, the latter with the validated questionnaire Voice Handicap Index (VHI), and performed standardized voice recordings. These recordings were analyzed in a controlled manner by a professional voice therapist. During the allergy season, patients reported more respiratory and voice symptoms compared with controls. Those with blinded scored voice dysfunction scored their voice quality during springtime as 31 mm (95% confidence interval [CI] 20-42 mm), compared with 13 mm (95% CI 6-21 mm for participants without voice dysfunction (P<0.01). Furthermore, the group with experienced voice dysfunction scored significantly higher on the VHI in the functional and physical domains and in the total VHI score. Although voice problems during the pollen season are rarely discussed, in allergic rhinitis the larynx may also be involved. These findings support that some patients experience voice change, an experience which can be objectively confirmed.

Relative frequencies of symptoms and risk factors among patients with chronic rhinosinusitis with nasal polyps using a case-control study.

OBJECTIVES: The aim of this study was to investigate the relative frequency of important symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), the link between CRSwNP and the lower airways and the importance of smoking in CRSwNP. METHOD: Three hundred and sixty-eight patients with CRSwNP and 1349 controls were recruited to the study and underwent a structured interview about symptoms from the upper and lower airways, and about smoking habits. Furthermore, all participants were clinically examined using nasal endoscopy. RESULTS: Due to interactions between the outcome variables, a multiple logistic regression model was fitted to the data. Nasal secretions, nasal blockage and impaired sense of smell were symptoms associated with CRSwNP. Furthermore, male gender, increasing age and asthma were also associated with the disease. Current smoking was less frequent among patients with CRSwNP. CONCLUSION: By comparing symptoms and risk factors of patients with CRSwNP with those of a large population-based control group and testing them in a multiple logistic regression model, we have been able to generate data that address key research interests in CRSwNP.

Clinical experience with patients with olfactory complaints, and their quality of life.

CONCLUSION: A special consulting team for patients with olfactory disorders would be able to verify, describe, and explain the characteristics of the disorders, also in cases where a patient experiences a disorder, but has a normal sense of smell. OBJECTIVES: The general purpose of this paper was to present our experience with patients seeking medical attention for olfactory disorders, and to describe how quantitative and qualitative olfactory disorders are diagnosed, what the etiologies are, and how quality of life is compromised in patients with olfactory disorders. SUBJECTS AND METHODS: This investigation was performed prospectively over a 10-year period by one physician responsible for the consulting team for patients with olfactory disorders. Based on a standardized clinical examination, a structured interview, and assessment of olfactory function, its aim was to diagnose quantitative and qualitative disorders in 303 consecutive patients. Health-related quality of life was assessed with the Nottingham Health Profile (NHP) in about one-third of patients. RESULTS: In the majority of patients, a reduced sense of smell was found after testing. Often, but not always, this was combined with qualitative disorders. Dominating etiologies were infections, nasal polyposis, head trauma, and aging. Patients complaining of olfactory disorders experience a significantly reduced quality of life regarding the impact of their health problem on paid employment, household work, and social and family life.

Excessive obesity is related to daily symptoms of nasal blockage: the Skövde population-based study.

This study has as its focus on obesity as a factor of importance for nasal blockage. A random sample of 1.900 adults stratified according to age and gender were recruited from the general population. The study included a structured interview about symptoms of nasal blockage and asthma, and a clinical examination with nasal endoscopy. Smoking habits were evaluated by a questionnaire on current and previous smoking. A response rate of 73% was achieved. There was a statistically significant relationship between subjectively experienced daily nasal blockage and registered heavy overweight, but no relationship was found between nasal blockage and age, gender, diabetes or asthma. The odds ratio (OR) for individuals with excessive obesity to have daily symptoms of nasal blockage was 3.7 [95% CI 1.6-7.6]. In patients with nasal blockage, obesity as a cause should be taken into consideration.

Prevalence of parosmia: the Skövde population-based studies.

AIM: Parosmia can be defined as a qualitative odor distortion. Despite the consequences of this condition for quality of life, the scientific literature lacks information about the prevalence of parosmia in the general population, which was the objective of the present study. METHODS: Random samples of 1,900 adult and 401 teenage inhabitants, stratified for age and gender, were drawn from the municipal population register of Skövde, Sweden. In total, 1,713 individuals (74% of the samples) agreed to participate, of which 1,387 (73%) were adults and 326 (81%) were teenagers. They responded to a question about parosmia by means of either a structured interview (adults) or a questionnaire (teenagers). RESULTS: The overall prevalence of parosmia was 3.9% (4.0% in adults and 3.4% in teenagers), which was stable across gender, but differed somewhat between age groups, with highest prevalence in the age group 20-29 years. CONCLUSIONS: The rather high overall prevalence, 3.9%, does indeed suggest that parosmia deserves attention when attempting to better understand olfactory dysfunction in clinical settings and in the general population of both adults and teenagers.

A family-based genome-wide association study of chronic rhinosinusitis with nasal polyps implicates several genes in the disease pathogenesis.

BACKGROUND: The pathogenesis of chronic rhinosinusitis with nasal polyps is largely unknown. Previous studies have given valuable information about genetic variants associated with this disease but much is still unexplained. Our goal was to identify genetic markers and genes associated with susceptibility to chronic rhinosinusitis with nasal polyps using a family-based genome-wide association study. METHODS: 427 patients (293 males and 134 females) with CRSwNP and 393 controls (175 males and 218 females) were recruited from several Swedish hospitals. SNP association values were generated using DFAM (implemented in PLINK) and Efficient Mixed Model Association eXpedited (EMMAX). Analyses of pathway enrichment, gene expression levels and expression quantitative trait loci were then performed in turn. RESULTS: None of the analysed SNPs reached genome wide significant association of 5.0 x 10-8. Pathway analyses using our top 1000 markers with the most significant association p-values resulted in 138 target genes. A comparison between our target genes and gene expression data from the NCBI Gene Expression Omnibus database showed significant overlap for 36 of these genes. Comparisons with data from expression quantitative trait loci showed the most skewed allelic distributions in cases with chronic rhinosinusitis with nasal polyps compared with controls for the genes HLCS, HLA-DRA, BICD2, VSIR and SLC5A1. CONCLUSION: Our study indicates that HLCS, HLA-DRA, BICD2, VSIR and SLC5A1 could be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. HLA-DRA has been associated with chronic rhinosinusitis with nasal polyps in previous studies and HLCS, BICD2, VSIR and SLC5A1 may be new targets for future research.

Role of the upper airways in patients with chronic cough.

PURPOSE OF THE REVIEW: Chronic cough can be caused by a number of factors, including infections, rhinosinusitis, asthma and environmental stimuli. This paper reviews recent findings and opinions regarding the role played by the upper airways in chronic cough. RECENT FINDINGS: Chronic cough has a significant impact on quality of life, which is more pronounced in women. In Western countries, the reported occurrence of rhinosinusitis in patient groups with chronic cough ranges from 8% to 81%. Allergic rhinitis is a risk factor for later development of asthma. In children, bronchiectasis is combined with upper airway abnormalities in the majority of cases. Increased expression of the capsaicin receptor subtype named 'transient receptor potential vanilloid-1', which correlates with capsaicin cough response, has been identified in patients with chronic cough. Patients with airway chemical sensitivity and chronic cough as one symptom have augmented capsaicin cough sensitivity that is related to changed levels of nerve growth factor in nasal lavage. SUMMARY: Involvement of the upper airways in chronic cough has been confirmed in several studies. However, there are considerable differences between different health centres in the occurrence of rhinosinusitis as a cause of chronic cough. In patients with chronic cough of various causes, a neurochemical alteration in both the upper and the lower airways appears to have taken place, followed by increased cough sensitivity.

Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence.

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between the behavioral consequences of self-reported odor sensitivity with the chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) and cough sensitivity to inhaled capsaicin. We also wanted to estimate the prevalence of airway sensory hyperreactivity (SHR), which was defined as a positive CSS-SHR score in combination with a positive capsaicin inhalation test result. DESIGN: A general population-based study with randomly selected individuals after stratification for age and gender. SETTING: Skövde Central Hospital, Departments of Lung Medicine and Otorhinolaryngology, Sweden. PARTICIPANTS: A total of 693 randomly selected individuals from a population-based study in which 595 persons (86%) responded to the CSS-SHR questionnaire. INTERVENTIONS: The individuals were divided into four groups with different odor sensitivity according to their CSS-SHR score. Of these, 137 individuals were randomly recruited for the capsaicin inhalation test. Capsaicin inhalation was performed with concentrations of 0.4 and 2.0 mumol/L in a randomized order. The number of coughs were registered and counted for 10 min from the start of each inhalation. MEASUREMENTS AND RESULTS: Of the 137 individuals who were recruited for the capsaicin inhalation test, 103 (75%) participated. Sixteen individuals had increased cough sensitivity and fulfilled the criteria for a positive capsaicin inhalation test result. Of the individuals with a positive capsaicin inhalation test result, > 80% also had a positive CSS-SHR score. Only 5% of the individuals with a negative CSS-SHR score had a positive capsaicin inhalation test result. The order of inhaled capsaicin concentration was found to influence the results. The prevalence of SHR with the definition given above was estimated to be 6.3% in this general population. CONCLUSIONS: A high CSS-SHR score was found to be directly related to the sensitivity for inhaled capsaicin, which made it possible to relate subjective data to objective findings.

Do topical nasal decongestants affect polyps?

CONCLUSIONS: The hypothesis that decongestants reduce the size of nasal polyps could not be verified. Decongestion is therefore recommended prior to nasal endoscopy, especially in polyp diagnosis, as it does not artificially change the size of the polyps. OBJECTIVE: The role of nasal decongestants in nasal stuffiness is well established and their action is well known. Decongestants are also used prior to nasal endoscopy to achieve a better view of the nasal cavity in order to diagnose polyps. The question is whether this decongestion invalidates the estimation of polyp size in clinical and scientific practice. The aim of this study was to evaluate possible effects of topical decongestants on polyp extension in patients with nasal polyposis. MATERIAL AND METHODS: The effect of the decongestants nafazoline and epinephrine on nasal polyp size was assessed by means of a double-blind, placebo-controlled randomized study. A sensitive endoscopic scoring system, lateral imaging, was used to assess the size and extension of the nasal polyps. RESULTS: No significant effect of decongestion on polyp size could be found for either treatment.

Prevalence of upper and lower airway symptoms: the Skövde population-based study.

CONCLUSION: This study was able to present representative data from Sweden as a whole and illuminates the epidemiological background of symptoms of the upper and lower airways. Current regular smokers, compared with non-smokers, had more problems with nasal blockage, cough and asthma. The relationship between the upper and lower airways was confirmed as regards airway symptoms. BACKGROUND: Epidemiology of common respiratory symptoms is basic information in health care. This study has focused on the prevalence of upper and lower airway symptoms. PATIENTS AND METHODS: A random sample of 1900 age- and gender-stratified adults was recruited from a general population for this study, which included a structured interview about symptoms of nasal secretions and blockage, cough and asthma, and a clinical examination with nasal endoscopy, and peak nasal-inspiratory flow (PNIF). Smoking habits were evaluated by a questionnaire for current and previous smoking. RESULTS: A response rate of 73% was achieved. The prevalence of various symptoms varied between age strata and gender. There was a statistically significant relationship between subjectively experienced nasal blockage and objectively observed nasal congestion. PNIF was negatively related to age and height and was increased in male gender. Smoking was most common among females and related to nasal blockage, cough and asthma, but not to nasal secretions. Significant relationships between the upper and lower airways were found.

What Happens With Untreated Nasal Polyps Over Time? A 13-Year Prospective Study.

OBJECTIVES: Nasal polyps are often seen in ENT practice, but little is known about the pathogenesis and the natural development. Our objective was to follow individuals with untreated nasal polyps prospectively, in terms of polyp size, symptoms, and respiratory function. METHODS: Thirty-three individuals, aged 27 to 87 years, with untreated nasal polyps were identified in a population-based study. Peak nasal inspiratory flow, olfactory function, and size of the nasal polyps were examined. Respiratory symptoms were also registered. Follow-up examinations were performed after 6 and 13 years, with change between visits analyzed. RESULTS: Over time, polyp size as well as occurrence of unilateral or bilateral polyps varied without an obvious pattern, with no consistent trends in respiratory function or symptoms. Twenty-one individuals (64%) were still untreated at the 6-year follow-up, and 12 (36%) remained untreated during the whole 13-year follow-up. Dropouts were due mainly to death. Seven individuals (21%) started treatment during the follow-up and had larger polyps and more subjective respiratory symptoms at baseline compared to the untreated group. CONCLUSION: Nasal polyps found occasionally are often part of a chronic entity but do not necessarily evolve into a more serious condition over time. Treatment should therefore be based on the patients' subjective problems.

Changes in levels of nerve growth factor in nasal secretions after capsaicin inhalation in patients with airway symptoms from scents and chemicals.

Patients complaining of upper and lower airway symptoms caused by scents and chemicals have previously been shown to have increased cough sensitivity to inhaled capsaicin, but the precise mechanisms behind this reaction are unknown. Hypothesizing that a neurochemical alteration related to sensory hyperreactivity (SHR) of the airway mucosa occurs, we measured levels of nerve growth factor (NGF) in nasal lavage fluid (NAL) before and after capsaicin inhalation provocations and related the capsaicin cough sensitivity to the NGF levels. Thirteen patients with SHR and 14 control subjects were provoked with capsaicin inhalation at three different doses. We measured NGF in NAL before and after provocation and recorded cough and capsaicin-induced symptoms. All subjects demonstrated a dose-dependent cough response to capsaicin inhalation, with a more pronounced effect in patients than in controls. Basal levels of NGF were significantly lower in the patient group than in the control subjects (p < 0.01). After capsaicin provocation, the patients showed a significant increase in NGF (p < 0.01), which was related to capsaicin cough sensitivity. The findings demonstrate that, in patients with airway symptoms induced by scents and chemicals, SHR is real and measurable, demonstrating a pathophysiology in the airways of these patients compared to healthy subjects.

Chemosensory perception and event-related potentials in self-reported chemical hypersensitivity.

Anormal chemosensory perception has been identified as a possible mechanism underlying odor intolerance, but research in this domain has yet been rather limited. The main objective of the present study was to investigate total perceived intensity, unpleasantness, sensory irritation, and cortical activity assessed with chemosensory event-related potentials (ERPs) for three concentrations of pyridine ranging from predominantly olfactory to trigeminal in activation. Results from 19 individuals with self-reported chemical hypersensitivity and 19 controls with self-reported normal chemical sensitivity show that the hypersensitive group, compared to controls, rated the pyridine stimuli to be more intense and unpleasant, and that these group differences increased with pyridine concentration. Sensory irritation was also the perceptual dimension found to correlate strongest with score on the chemical sensitivity scale. However, no group differences were found in ERP amplitudes or latencies. These findings suggest that self-reported chemical hypersensitivity (1) can be associated with anormal chemosensory perception, (2) may be more closely related to trigeminal function than to olfaction, and (3) has a neural basis at a higher cortical level than that captured by chemosensory ERPs.