ASSOCIATION BETWEEN SYMPTOM SEVERITY AND INTENSITY OF ACUTE PSYCHOLOGICAL DISTRESS IN NEWLY DIAGNOSED PATIENTS WITH CHRONIC RHINITIS AND CHRONIC RHINOSINUSITIS.

Chronic rhinitis and rhinosinusitis (CR and CRS) can lead to impairment of the health-related quality of life (HRQL) with higher psychological perceived distress, resulting in disease worsening and poor treatment outcomes. W aimed to evaluate the potential association between disease severity and HRQL impairment with the perceived acute psychological distress in newly diagnosed CR/CRS patients. This single-center cross-sectional study included otherwise healthy consecutive adults with newly diagnosed CR/CRS (European position paper on rhinosinusitis and nasal polyp criteria and International Consensus Statement on Allergy and Rhinology - Allergic Rhinitis criteria or non-allergic rhinitis), who were evaluated for CR/CRS symptom severity and HRQL (Sino Nasal Outcome Test 22 [SNOT-22], visual analog scale [VAS]) and acute perceived distress (Perceived Stress Scale [PSS]). Principal component analysis (SNOT-22 items, VAS) identified 6 components as CR/CRS severity indicators, i.e,, poor sleep, wakes-up tired, nasopharynx, obstruction, torment and rhinorrhea, which were evaluated for association with PSS score. Of the 63 included patients (20 men, age median 38, range 19-75 years), 27 suffered from CR and 36 from CRS. Upon adjustment for age and sex, higher total SNOT-22 (geometric means ratio [GMR]=1.04, 95% CI 1.01-1.06), higher "torment" (GMR=1.13, 1.04-1.24), higher "poor sleep" (GMR=1.11, 1.02-1.21) and higher "wakes-up tired" (GMR=1.11, 1.01-1.21) scores were each associated with a higher PSS score, overall and consistently in CR and CRS patients. In conclusion, more severe CR/CRS is associated with greater perceived psychological distress already at earlier stages of the disease. Paying attention to patient level of distress and anxiety over time may enable better understanding of the connection between exacerbations, symptom severity and psychological burden of the disease.

In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery.

In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery.

UNILATERAL VS. DIFFUSE CHRONIC RHINOSINUSITIS.

Chronic rhinosinusitis (CRS) is a widespread disease with various symptoms. It is defined as an inflammation of the nasal mucosa and paranasal sinuses lasting for 12 weeks, with symptoms of nasal obstruction and/or congestion and facial pain and/or pressure as well as decreased sense of smell. Despite the widespread prevalence of the disease, the diagnosis and treatment of CRS are still not adequately developed, so many patients remain misdiagnosed. This study involved 150 patients who, according to EPOS guidelines, met the diagnosis of CRS without nasal polyposis. Each patient underwent a computerized tomography (CT) scan of the paranasal sinuses, which was evaluated according to the Lund-Mackay scoring system. Furthermore, patients completed a visual analog scale (VAS) score questionnaire which examined the severity of their symptoms. The aim of this study was to find an association between the degree of mucositis and the clinical symptoms reported by the patient. Our results showed a low positive correlation between nasal secretion and Lund-Mackay score for the bilateral ostiomeatal complex (OMC). Furthermore, a low positive correlation was found between the severity of reduced sense of smell and severity of anterior ethmoid and sphenoid sinusitis. The results demonstrated a low negative correlation between the severity of facial pain or pressure and the severity of inflammation of the anterior ethmoid and sphenoid sinus. The results of statistical testing did not show statistical differences in severity of subjective symptoms for almost all of the observed symptoms in persons with unilateral inflammation and persons without unilateral inflammation, except for cough. People who did not have unilateral inflammation had a more pronounced cough compared with people who had unilateral inflammation. However, these correlations were very mild and not clinically significant, so we cannot say that the distribution of sinusitis significantly affects the occurrence of characteristic symptoms in chronic rhinosinusitis.

Imaging in chronic rhinosinusitis: A systematic review of MRI and CT diagnostic accuracy and reliability in severity staging.

BACKGROUND: Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. PURPOSE: The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. MATERIAL AND METHODS: This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, "severity staging", "diagnostic accuracy "and "imaging "resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. RESULTS: CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. CONCLUSIONS: MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.

The impact of asthma on quality of life and symptoms in patients with chronic rhinosinusitis.

Objective: The study aims to evaluate how asthma influences on clinical symptoms, imaging scores and HRQL in CRS patients.Methods: The study enrolled CRS patients and collected data about asthma status, clinical symptoms, allergic sensitization, computed tomography (CT) and 22-item SinoNasal Outcome questionnaire (SNOT-22). Matching pairs of asthmatic and non-asthmatic CRS patients were defined based on age, gender and nasal polyp presence. The difference between pairs in clinical symptoms, CT and SNOT-22 was then analyzed. The study enrolled mild to moderate asthma patients.Results: From 250 CRS patients 65 (26%) had asthma. We found 60 CRS asthma and CRS non-asthma pairs based on age, gender and nasal polyp presence. There was no difference in total SNOT-22 score between asthma (46.5) and non-asthma (43.5) CRS groups (p < .357). There were more patients with allergy positive medical history in asthma group (66.1%) when we stratified for CRS phenotypes, gender and age. Comparing visual analogue scale (VAS) scores for clinical symptoms, smell (p < .013) was the only symptom significantly worse in CRS asthma group. Although there was no difference in Lund-Mackay score, there was a slightly higher osteitis score in CRS asthma group (5.21 vs. 3.45; p = .059).Conclusion: CRS patients with asthma have significantly worse impairment of smell and taste when compared to non-asthmatic CRS patients. This is the only significant difference which is independent of nasal polyp presence, gender, age and allergy.

Hierarchical clustering in evaluating inflammatory upper airway phenotypes; increased symptoms in adults with allergic multimorbidity.

BACKGROUND: Inflammatory upper airway diseases cause significant morbidity. They include phenotypes with different treatment; allergic or non-allergic rhinitis (AR, nAR), and chronic rhinosinusitis with or without nasal polyps (CRSwNP, CRSsNP). In clinical practice, these phenotypes are often difficult to distinguish and may overlap. OBJECTIVE: To evaluate if hierarchical clustering can be used to distinguish these phenotypes based on the presence of nasal polyps, off-seasonal allergic symptoms, and self-reported background characteristics - e.g. atopic dermatitis (AD); and to further analyse the obtained clusters. METHODS: We studied a random sample of 74 CRS (chronic rhinosinusitis) patients, and a control group of 80 subjects without CRS with/without AR (tertiary hospitals, 2006-2012). All underwent interview and nasal examination, and filled a questionnaire. Variables regarding demographics, off-seasonal symptoms, and clinical findings were collected. Hierarchical clustering was performed, the obtained clusters were cross-tabulated and analysed. RESULTS: Four clusters were identified; 1: "Severe symptoms and CRSwNP" (n = 29), 2: "Asymptomatic AR and controls" (n = 39), 3: "Moderate symptoms and CRSsNP" (n = 36), and 4: "Symptomatic and AD" (n = 50). Cluster 1 had most sinonasal symptoms, cluster 3 had a high prevalence of facial pain. The presence of AR did not distinguish CRS groups. Of the AR subjects, 51 % belonged to cluster 4, where AR with off-seasonal airway symptoms and AD predominated. CONCLUSIONS: Hierarchical clustering can be used to distinguish inflammatory upper airway disease phenotypes. The AR phenotype was subdivided by the presence of AD. Adult AR+ AD patients could benefit from active clinical care of the upper airways also off-season.

Cluster Analysis of Chronic Rhinosinusitis Suggests Gender-Based Differences.

PURPOSE: We aimed to evaluate the interaction between the overall severity of chronic rhinosinusitis (CRS) before treatment and subjective improvement following surgical or medical treatment. PROCEDURES: A group of 97 patients with CRS completed the visual analog scale (VAS) symptom score and the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire in the moment of their sinus computerized tomography (CT) scan. Data were analyzed via a 2-step cluster analysis based on gender, polyp presence, CT scan, and VAS scores for symptoms. RESULTS: There were 3 clusters: the first cluster comprised 37 female patients with CRS without nasal polyps (CRSsNP), the second cluster comprised 30 patients with CRS and NP (CRSwNP; 15 males and 15 females); and third cluster had 30 male patients with CRS without NP (CRSsNP). Different symptom patterns between clusters were identified. After adjustment for polyp presence, gender, eosinophilia (p = 0.021), and the SNOT-22 score (p = 0.005) were found to be better outcome predictors than the CT score (p = 0.26). CONCLUSION: Long-term patient satisfaction is significantly associated with the subjective symptom severity prior to treatment, i.e., postnasal drip and overall disease severity (SNOT-22 score), but not with the objective severity of the disease (CT score and inflammation).

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough.

Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps.

Objective of this study was to test whether there is a difference between chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps in the association of extent of disease on CT scans with symptom severity and health-related quality-of-life (HRQL) impairment. Data sets from 271 chronic rhinosinusitis (CRS) patients who completed the Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scores were subjected to principal component analysis (PCA) to identify a symptom components related to CRS. After controlling for demographics, medical therapy, and comorbidities, the association between symptom components/items excluded from PCA and Lund-Mackay score (LMS) was evaluated. No association was found between the total SNOT-22 score and LMS in CRS patients. There was an independent association between a higher "nasal" symptom component derived from SNOT-22 PCA and LMS in patients with CRSwNP (p < 0.001), but not in CRSsNP patients, with a statistically significant difference between two patient subsets (p = 0.003). In patients with CRSsNP, higher (worse) SNOT-22 "facial pain" was associated with lower LMS (p = 0.022), although the estimated change in LMS was modest. Considering VAS PCA components, higher "nasal" symptoms were associated with higher LMS in CRSwNP patients (p < 0.001) but not in CRSsNP, with a statistically significant difference between CRS groups (p = 0.024). A higher "pain" PCA component was associated with lower LMS in CRSsNP patients (p = 0.019). This study found significant differences in the relationship between symptom burden and CT scores between CRS phenotypes and no association between HRQL impairment and CT scores.

Differences in the Sino-Nasal Outcome Test 22 and visual analog scale symptom scores in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) with and without polyps has a high impact on health-related quality of life (HRQL), but the difference in HRQL and symptom presentation between two clinical phenotypes of CRS has not been specifically evaluated before now. OBJECTIVE: To evaluate patterns of symptoms and HRQL disease-specific domains affected in patients with CRS by comparing differences between two clinical phenotypes, adjusted for demographics, major risk factors, comorbidities, current medical treatment, and previous surgery. METHODS: A group of 251 patients with CRS completed the visual analog scale (VAS) symptom severity score and the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire. Data sets were analyzed by using principal component analysis (PCA) to identify a set of symptom components, together with the items excluded from PCA, which were then analyzed for differences between patients with CRS with nasal polyps (CRSwNP) and patients with CRS without nasal polyps (CRSsNP). RESULTS: PCA of SNOT-22 items identified six components, three referred to CRS-specific symptoms termed "nasal"; "extranasal, rhinologic"; and "olfactory/cough"; and three referred to HRQL impairment termed "sleep disturbance," "functional disturbance," and "emotional disturbance." Nasal obstruction, ear pain, ear fullness, and fatigue were excluded from PCA and treated as separate outcomes. Patients with CRSwNP had significantly worse nasal symptoms, olfactory/cough symptoms, and nasal obstruction. Patients with CRSsNP scored significantly worse with regard to fatigue and to sleep and functional disturbances. The PCA results for VAS scores identified three symptom components: pain, nasal symptoms, and pharyngeal symptoms. Patients with CRSwNP had significantly worse VAS nasal symptoms but less pronounced VAS pain symptoms than patients with CRSsNP. The total SNOT-22 score between the groups was not significantly different. CONCLUSION: With controlling of covariates that may influence the severity of the disease, this study showed significant differences in symptom patterns and different aspects of HRQL impairment between patients with CRSwNP and patients with CRSsNP, however, with no difference in the total HRQL score.

Septoplasty in children.

OBJECTIVES: Physicians have long had concerns about the potential harmful effects of pediatric septoplasties on the nasoseptal growth process because septal cartilage is important for the growth and development of the face. METHODS: In this review article, pediatric septoplasty and its indications are discussed, together with a literature survey. In addition, overviews of development of the nasal skeleton from neonate to adult, nasal growth, and cartilaginous septum are presented. Important issues and comments on pediatric septoplasties are provided. RESULTS: During septoplasty procedures, elevation of the mucoperichondrium unilaterally or bilaterally does not negatively affect growth of the face. Stabilization of the septum may be easier when mucosal elevation is performed unilaterally. The nasal floor mucosa should not be elevated so to avoid damage to the incisive nerves. Corrections and limited excisions may be done from the cartilaginous septum. Separation of the septal cartilage from the perpendicular plate, especially at the dorsal part, should not be performed because this area is important for the length and height of the nasal septum and nasal dorsum. Incisions or excisions should not be performed through the growing and supporting zones, especially at the sphenoethmoid dorsal zone. CONCLUSION: If there are severe breathing problems related to the septal deviation, septoplasty should be performed. In the majority of cases, septal surgery may be conducted in 6-year-old children. However, if necessary, septal surgery may be performed in younger children and even at birth.

Relationship between nasal septal deformity, symptoms and disease severity in chronic rhinosinusitis.

The objective of this study was to evaluate the interaction of nasal septal deformity (NSD), including the contribution of septal spurs, with the severity of subjective symptoms, impairment of health-related quality of life (HRQoL) and sinus mucosal hyperplasia in patients with chronic rhinosinusitis (CRS). One hundred seventeen patients with CRS were assigned to three groups with mild, moderate or severe NSD, according to the measured nasal septal angle, including the presence of contact septal spurs. All CRS patients completed the visual analog scale (VAS) symptom severity score and the Sino-Nasal Outcome Test (SNOT-22) questionnaire. Symptoms scores, SNOT-22 and Lund-Mackay (LM) scores among the three NSD groups were compared. Related anatomy from the study group was compared with 100 control patients. VAS score for postnasal discharge in CRS patients was significantly higher in patients with mild NSD. There was a significantly higher LM score in CRS patients with severe NSD, compared to those with mild (P = 0.001) or moderate NSD (P = 0.005). CRS patients with a contact spur demonstrated a significantly higher LM score (P = 0.006) compared to those without a contact spur, and no differences in VAS symptom scores or HRQoL scores. There was a similar prevalence of septal deformities in CRS patients and in the non-ENT population. Our results support the conclusion that in patients with CRS, associated NSD or contact septal spur do not contribute significantly to CRS symptom severity or HRQoL impairment, but may have an impact on sinus mucosal hyperplasia.

Surgical treatment for nasal polyposis: predictors of outcome.

Nasal polyps recur in approximately one-third of patients after surgical treatment. It would be beneficial to be able to predict the patients in whom we might expect recurrence and to predict the clinical outcome after surgery. The study included 30 patients operated for nasal polyps. Removed polyps were analyzed by immunohistochemical analysis for IL-5, IgE, vascular endothelial growth factor and eosinophilic infiltration. These parameters together with preoperative CT score were used as independent variables, and subjective score improvement after 2 years was used as a dependent variable in multiple linear regression analysis. Furthermore, the patients were divided into two groups: low and high polyp tissue immunoreactivity. The Chi-squared test was used to determine whether polyp immunoreactivity influences polyp recurrence and subjective score. Preoperative CT score had a slightly positive correlation with subjective score after 2 years. High eosinophil infiltration significantly predicted a higher risk for polyp recurrence. High IL-5 positivity was related to greater risk for polyp recurrence than low IL-5 reactivity but not significantly. IgE and VEGF reactivity in polyp specimens did not have any effect on polyp recurrence. High eosinophilic infiltration in polyps can predict worse outcome after surgical treatment of chronic rhinosinusitis with nasal polyposis. IgE and VEGF do not have prognostic significance to polyp recurrence after surgery. The preoperative extent of disease measured by CT score had a slightly positive correlation with worse outcome after surgery.

Perceived stress and severity of chronic rhinosinusitis in allergic and nonallergic patients.

Chronic stress exposure carries greater risk of onset of atopic respiratory disorders such as rhinitis and asthma. The interaction between depression, anxiety, and severity of chronic rhinosinusitis (CRS) has been suggested. We aimed to access the relationship between psychological stress, severity of CRS, and atopy. Sixty-three consecutive patients referred with CRS were asked to score the severity of rhinosinusitis symptoms on a visual analog scale and to fill in questionnaires on the disease-specific quality of life and perceived stress-22-item Sino-Nasal Outcome Test (SNOT-22) and measure of perceived stress (MPS) scale, respectively. Inclusion criteria for the study were a reliable allergy evaluation and a recent computerized tomography (CT) scan of the sinuses. Patients with nasal polyps (NPs), asthma, and previous surgery were excluded. The study group consisted of 14 allergic and 18 nonallergic patients with CRS without NPs (CRSsNPs). Correlation between MPS and SNOT-22 scores in the study group was highly significant (Pearson r = 0.61; p = 0.001). Patients with higher stress scores had significantly stronger postnasal discharge, thick discharge, cough, disturbed sleep, fatigue, and sadness. Postnasal drip was significantly stronger in patients with allergy. The correlation between SNOT-22 and CT scores was insignificant. The correlation between MPS and SNOT-22 scores suggests an interaction between severity of CRS and chronic stress, but not with the extent of the disease on CT in CRSsNPs. Chronic psychological stress might be one of the factors that modifies the disease severity and may lead to uncontrolled disease in CRS patients.

Evolution of guidelines for pediatric rhinosinusitis.

Rhinosinusitis is a prevalent disorder in the pediatric population. Unfortunately, during the past two decades, guidelines related to definitions, diagnostic procedures and management have been much more focused on adult than on pediatric rhinosinusitis. First consensus document on management of pediatric rhinosinusitis was published in 1998, followed by several documents related only to acute rhinosinusitis. The most extensive consensus document on rhinosinuistis, including pediatric rhinosinusitis, is European position paper on rhinosinusitis and nasal polyps, EPOS, updated in 2012.

European Position Paper on Rhinosinusitis and Nasal Polyps 2012.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007.The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed.

EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Management of Smell Dysfunction.

Olfaction is an essential chemosensory system in the living world. Although less appreciated in humans, smell impairment significantly affects many aspects of quality of life. Smell disorders may be caused by an impaired nasal airway or by lesions in the olfactory system, leading to reduced or distorted smell perception. The most common causes of smell disorders are aging, upper respiratory tract infection, sinonasal disease, and head trauma. Recovery is rarely complete. Counseling is important in progressive or severe smell loss. In patients with distorted smell perception, antidepressant medication is sometimes necessary. Best response to treatment is achieved for nasal obstruction and sinonasal inflammatory disease. Treatment of olfactory impairment caused by sinonasal disease includes medication with topical and systemic steroids, or surgery for refractory cases. Although there are reports that surgical resection of olfactory neurons may lead to reinnervation and recovery of smell, adequate treatment of the smell loss remains an unmet need.

Recurrent sinonasal melanoma--report of five surgical cases and short literature review.

The aim of this study is to present five surgical cases of recurrent sinonasal melanoma. We report the clinical course of this highly malignant disease and give a brief overview of the relevant literature. For the purpose of our presentation, inclusion criteria for all patients were initally negative surgical margins, surgery with curative intent without implementation of radiotherapy, and absence of distant metastatic spread at presentation (MO). They were diagnosed and treated at the same ENT/Head and Neck Surgery department and had clear surgical margins following first resection. The majority of five cases had local recurrences (average two) which were all amenable to at least one salvage operation. In conclusion, despite extensive disease at presentation, we recommend repeated attempts at local surgical salvage. However, this decision must be carefully considered, respecting postoperative quality of life, the estimated life expectancy as well as general socioeconomic issues in each particular case.

Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance.

BACKGROUND: Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact. OBJECTIVE: The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils. METHODS: Tonsil allergen-specific FOXP3(+) regulatory T (Treg) cells, plasmacytoid dendritic cells (pDCs), and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining, [(3)H]-thymidine incorporation, and carboxy-fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy. RESULTS: CD4(+)FOXP3(+) Treg cells and pDCs constitute important T- and dendritic cell-compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4(+)CD25(+)CD127(-)FOXP3(+) Treg cells with suppressive property from naive T cells. CD4(+)FOXP3(+) Treg cells proliferate and colocalize with pDCs in vivo in T-cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3(+) Treg cells enables the allergen-induced proliferation of tonsil T cells, indicating an active role of Treg cells in allergen-specific T-cell unresponsiveness. High numbers of major birch pollen allergen, Bet v 1-specific CD4(+)FOXP3(+) Treg cells, are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3(+) Treg cells and pDCs is observed in tonsils from nonatopic individuals. CONCLUSION: Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.