[Prehospital care of anaphylactic reactions by the air rescue and ground-based emergency services Dresden : An analysis of treatment and outcome]. / Präklinische Versorgung von anaphylaktischen Reaktionen durch die Dresdner Luft- und Bodenrettung : Analyse von Therapie und Outcome.

BACKGROUND: Anaphylaxis can lead to a life-threatening situation. Therefore, rapid diagnosis and emergency treatment is indicated. Immediate treatment with intramuscular adrenaline (or intravascularly with sufficient medical expertise) in anaphylaxis with cardiovascular and/or respiratory symptoms is recommended by various guidelines. Previous studies have shown that anaphylaxis is often not treated according to guidelines and that adrenaline in particular is rarely administered. OBJECTIVE: The aim of the study was to investigate the data on emergency treatment and outcomes of patients with anaphylaxis by the air rescue and ground-based emergency services Dresden. Moreover, the results of the air- and ground-based services were compared. The focus was on administration of adrenaline and outcomes. MATERIALS AND METHODS: Data from the ground-based emergency service Dresden (from 2012 to 2016) and the air rescue service Dresden (from 2008 to 2015) related to anaphylactic reactions were analyzed retrospectively. The severity of the anaphylaxis, the emergency medication administered, further monitoring, and outcomes were analyzed. RESULTS: Data from 152 adults/29 children were analyzed for air rescue and 1131 adults/223 children for the ground-based emergency service. Adults with grade II-IV anaphylaxis received adrenaline in 19% (air rescue) and 7% (ground rescue) of cases. Children with grade II-IV anaphylaxis received adrenaline in 7% (air rescue) and 8% (ground rescue) of cases. Immediate drug therapy led to an improvement in general condition in 96-98% (air rescue) and 72-77% (ground-based emergency service) of cases. A significant correlation was found between the administration of adrenaline and the improvement in outcome in the ground-based emergency cohort. CONCLUSION: Guideline-compliant first-line therapy with adrenaline was not performed in the majority of the cases analyzed in this study. The significant effect of adrenaline on outcome demonstrated in this study emphases the need to improve the emergency treatment of anaphylactic reactions.

[Allergen immunotherapy for rare allergens]. / Allergen-Immuntherapie gegen seltenere Allergene.

Among allergies to aeroallergens, approximately 20% are allotted to the so-called rare allergens. These include ash pollen, weed pollen, storage mites, molds, and animal allergens. The prevalences of allergies to these allergens are lower, but affected patients also suffer considerably from their "rare" allergy. Hence, these allergies should neither be overseen nor completely forgotten in daily practice. Especially mold, mite, and animal allergens often induce asthma, so that the significance of allergen-specific immunotherapy (AIT) should not be neglected in causal therapy. This work summarizes the current state of knowledge on the groups of rare aeroallergens in terms of characteristics, prevalences, and data on AIT. It is based on a systematic literature search performed in the MEDLINE (PubMed®) and Google Scholar databases. AIT preparations for rare allergens are classified as individual formulations and are not subject to the German Therapy Allergen Ordinance. Due to the low case numbers, the levels of evidence for these formulations are not as high as those for dust mites, grass, or birch pollen, but exhibit good efficacy in practical experience.

Eosinophil granulocytes in chronic inflammatory respiratory diseases and CRSwNP: Function, immunological basis, and clinical significance.

INTRODUCTION: Eosinophils play an important regulatory and immunomodulatory role in airway mucosa and have antiparasitic and antiviral properties as well as pro-inflammatory effects that may also cause persistence of inflammation with tissue remodeling. The number of eosinophils and the detection of specific mediators in biological samples from, e.g., blood, nasal secretions, and bronchial fluid can serve as biomarkers that reflect the underlying pathophysiology of certain diseases, predict treatment success, and detect therapy effects. MATERIALS AND METHODS: A literature search was conducted to determine the immunologic basis, mode of action, clinical significance, and available evidence for therapeutic approaches using eosinophil-targeted monoclonal antibodies by searching Medline, Pubmed, and the national and international trial database (ClinicalTrials.gov) and guideline registries as well as the Cochrane Library. Human studies published on the topic in the period up to and including 10/2023 were considered. RESULTS: Based on the international literature and previous experience, the results are summarized, and recommendations are given. CONCLUSION: The important role of eosinophils in immunological processes in the airway mucosa is comprehensively analyzed and can serve as a basis for current and future treatment approaches.

EGPA: Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) as a special presentation of chronic rhinosinusitis with nasal polyps (CRSwNP).

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) was formerly known as Churg-Strauss syndrome. The condition is characterized by disseminated necrotizing vasculitis with extravascular granulomas associated with hypereosinophilia. The vasculitides affect small vessels and are associated with antineutrophil cytoplasmic antibodies (ANCAs) detectable in the blood. Distinguishing between type 2-mediated chronic airway inflammation such as chronic rhinosinusitis with nasal polyps (CRSwNP) without vasculitis can be clinically challenging and should be considered. MATERIALS AND METHODS: Immunological background, diagnosis, and therapy of EGPA were identified through literature searches in Medline, PubMed, as well as national and international studies (ClinicalTrials.gov) and the Cochrane Library. Human studies published up to and including 10/2023 on the topic were considered. RESULTS: In cases of deteriorating general health with previously known eosinophilic inflammation of the upper and lower airways, EGPA and its interdisciplinary investigation should be considered. Various types of eosinophilic inflammation and syndromes must be considered differentially. CONCLUSION: Characterization of mucosal airway inflammation through biomarker determination is meaningful and occasionally makes the difference for targeted therapy.

Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

The pharmacotherapeutic management of allergic rhinitis in people with asthma.

INTRODUCTION: Up to 90% of asthmatic patients have comorbid allergic rhinitis (AR). Although appropriate therapy of AR can improve asthma symptoms and management, AR is often underdiagnosed and under-treated in asthmatics.A non-systematic literature research was conducted on AR as a comorbidity and risk factor of asthma. Latest international publications in medical databases, international guidelines, and the Internet were reviewed. AREAS COVERED: Based on the conducted literature research there is proved evidence of the necessity of diagnosis and treatment of AR in patients with asthma because it affects health care utilization. Therefore, it is recommended in national and global guidelines. EXPERT OPINION: AR increases the risk of asthma development and contributes to the severity of an existing asthma. Early treatment of AR with drugs as intranasal steroids, antihistamines, leukotriene receptor antagonists, and especially allergen-specific immunotherapy can reduce the risk of asthma development and the concomitant medication use in addition to severity of symptoms in AR and asthma.

A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids.

BACKGROUND: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis. METHODS: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. RESULTS: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). CONCLUSION: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Two-Year Outcomes After Radiofrequency Neurolysis of Posterior Nasal Nerve in Chronic Rhinitis.

OBJECTIVE: To assess the long-term safety and effectiveness of temperature-controlled radiofrequency (TCRF) neurolysis of the posterior nasal nerve (PNN), a minimally invasive treatment for chronic rhinitis. METHODS: A prospective, single-arm study of 129 patients at 16 centers (United States, Germany) was conducted. Patient-reported outcome measures were the 24-h reflective total nasal symptom score (rTNSS) and mini rhinoconjunctivitis quality of life questionnaire (MiniRQLQ). Postnasal drip and cough symptoms were assessed using a 4-point scale. RESULTS: The mean pretreatment rTNSS was 7.8 (95% CI, 7.5-8.1). The significant rTNSS treatment effect at 3 months (-4.2 [95% CI, -4.6 to -3.8]; p < 0.001) was sustained through 2 years (-4.5 [95% CI, -5.0 to -3.9]; p < 0.001), a 57.7% improvement. At 2 years, the proportion of patients with a minimal clinically important difference (MCID) of ≥30% improvement in rTNSS from baseline was 80.0% (95% CI, 71.4%-86.5%). Individual postnasal drip and cough symptom scores were significantly improved from baseline through 2 years. The proportion of patients who reached the MCID for the MiniRQLQ (≥0.4-point improvement) at 2 years was 77.4% (95% CI, 68.5%-84.3%). Of 81 patients using chronic rhinitis medications at baseline, 61.7% either stopped all medication use (28.4%) or stopped or decreased (33.3%) use of ≥1 medication class at 2 years. No device/procedure-related serious adverse events were reported throughout 2 years. CONCLUSION: TCRF neurolysis of the PNN resulted in sustained improvements in chronic rhinitis symptom burden and quality of life through 2 years, accompanied by a substantial decrease in medication burden. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2077-2084, 2024.

Correlations between gustatory, trigeminal, and olfactory functions and nasal airflow.

PURPOSE: To determine the relationship of chemosensory screening and nasal airflow tests among the same set of participants, and to determine other factors that are related to the outcomes of these tests. METHODS: Participants had no chemosensory complaints. Structured medical history was taken. Participants underwent 5 screening tests: q-sticks (orthonasal olfaction), q-powders (retronasal olfaction), trigeminal lateralization test, taste sprays, and peak nasal inspiratory flow (PNIF). Ratings of smell/taste ability and nasal airflow were obtained using visual analogue scales (VAS). Composite sinusitis symptoms and significance of olfaction questionnaire scores were also determined. RESULTS: Four hundred participants were included in the study, 156 men, 244 women; aged 18-82 years (mean: 46). The q-powders and taste spray scores were weakly positively correlated with all the other chemosensory tests and PNIF. However, chemosensory test scores were not correlated with VAS, composite sinusitis symptoms, and significance of olfaction questionnaire scores. Various tests showed significant decrease starting at specific ages (in years, PNIF and trigeminal lateralization: 40, q-powders: 60, and q-sticks: 70). CONCLUSION: Chemosensory screening tests and self-rated chemosensory function showed no correlation in participants without chemosensory complaints. In addition, gustatory function appeared to be correlated with olfactory and trigeminal function but also with nasal airflow, and nasal airflow was related not only to olfactory but also to trigeminal and taste function. Over all, the results suggest that chemosensory functions (orthonasal olfactory, trigeminal, retronasal olfactory, gustatory) and nasal airflow are correlated with each other, which we propose may be possibly mediated, at least in part, through central nervous system interactions.

Trigeminal Sensitivity in Patients With Allergic Rhinitis and Chronic Rhinosinusitis.

OBJECTIVE: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC). METHODS: A total of 75 individuals participated (age 19-78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin' Sticks test battery. Trigeminal sensitivity was assessed with CO2 detection thresholds. Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO2 ) stimuli using high-precision air-dilution olfactometry. RESULTS: In comparison to HC, AR patients had lower CO2 thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC. CONCLUSION: AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:654-660, 2023.

Well-being in patients with olfactory dysfunction.

This cross-sectional, retrospective study aimed to investigate the differences in well-being among patients with olfactory disorder (OD) with quantitative and/or qualitative olfactory dysfunctions, and to identify factors associated with well-being (WB). We included 470 OD patients. WB (WHO-5 questionnaire), quantitative olfactory function (Sniffin' Sticks) and qualitative dysfunction were assessed. Overall, 35% of the OD patients reported a poor WB, higher than 22% of the normative data in general population. For quantitative function, anosmia patients showed lower WB scores than hyposmia and normosmia patients (all p's < 0.03). For qualitative dysfunction, patients with severe parosmia showed lower WB scores than patients without and with less severe parosmia (p's < 0.01). Regarding OD causes in hyposmic patients, post-infectious patients showed poorer WB than idiopathic patients (p = 0.01); sinonasal patients had lower WB than post-traumatic and idiopathic patients (all p's < 0.04). There was a weak but significant positive correlation between WB score and Threshold test score (r = 0.11, p = 0.02). Hierarchical regression analyses showed that women gender, Threshold and overall Sniffin' Sticks scores (TDI) significantly predicted WB score in OD patients. Our results implied that quantitative and qualitative dysfunction is associated with WB. However, only patients with severe dysfunction showed significantly lower WB. While this needs to be better understood, in order to improve well-being, in these patients it appears to be highly important to improve olfactory function, and here especially olfactory sensitivity.

Olfactory and gustatory disorders in COVID-19.

Loss of olfaction is one of the symptoms most commonly reported by patients with coronavirus disease 2019 (COVID-19). Although the spontaneous recovery rate is high, recent studies have shown that up to 7% of patients remain anosmic for more than 12 months after the onset of infection, leaving millions of people worldwide suffering from severe olfactory impairment. Olfactory training remains the first recommended treatment. With the continued lack of approved drug treatments, new therapeutic options are being explored. This article reviews the current state of science on COVID-19-related olfactory disorders, focusing on epidemiology, pathophysiology, cure rates, currently available treatment options, and research on new treatments.

Epithelial immune regulation of inflammatory airway diseases: Chronic rhinosinusitis with nasal polyps (CRSwNP).

BACKGROUND: The epithelial immune regulation is an essential and protective feature of the barrier function of the mucous membranes of the airways. Damage to the epithelial barrier can result in chronic inflammatory diseases, such as chronic rhinosinusitis (CRS) or bronchial asthma. Thymic stromal lymphopoietin (TSLP) is a central regulator in the epithelial barrier function and is associated with type 2 (T2) and non-T2 inflammation. MATERIALS AND METHODS: The immunology of chronic rhinosinusitis with polyposis nasi (CRSwNP) was analyzed in a literature search, and the existing evidence was determined through searches in Medline, Pubmed as well as the national and international study and guideline registers and the Cochrane Library. Human studies or studies on human cells that were published between 2010 and 2020 and in which the immune mechanisms of TSLP in T2 and non-T2 inflammation were examined were considered. RESULTS: TSLP is an epithelial cytokine (alarmin) and a central regulator of the immune reaction, especially in the case of chronic airway inflammation. Induction of TSLP is implicated in the pathogenesis of many diseases like CRS and triggers a cascade of subsequent inflammatory reactions. CONCLUSION: Treatment with TSLP-blocking monoclonal antibodies could therefore open up interesting therapeutic options. The long-term safety and effectiveness of TSLP blockade has yet to be investigated.

Phase 3b randomized controlled trial of fevipiprant in patients with nasal polyposis with asthma (THUNDER).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with asthma, particularly of late onset. Current treatment options for CRSwNP have limitations, and there is an unmet need for other safe and effective therapies. OBJECTIVE: The aim of the THUNDER study was to determine the efficacy and safety of the prostaglandin D2 receptor 2 (DP2) antagonist fevipiprant in patients with CRSwNP and concomitant asthma, measured by improvement in nasal polyp score (primary end point), nasal congestion score, Sinonasal Outcome Test 22 score, and University of Pennsylvania Smell Identification Test score. METHODS: THUNDER was a phase 3b, randomized, multicenter, double-blind, placebo-controlled, parallel-group, 16-week study of fevipiprant 150 mg or 450 mg once daily versus placebo. All patients received intranasal mometasone furoate 200 µg daily. RESULTS: Ninety-eight patients were randomly assigned to fevipiprant 150 mg (n = 32), fevipiprant 450 mg (n = 34), or placebo (n = 32). Mean (SE) change from baseline in nasal polyp score at week 16 was 0.20 (0.224) for fevipiprant 150 mg, -0.10 (0.216) for fevipiprant 450 mg, and 0.14 (0.233) for placebo. Mean treatment difference was 0.05 (95% confidence interval, -0.59, 0.70; adjusted P = .979) for fevipiprant 150 mg versus placebo and -0.25 (95% confidence interval, -0.88, 0.39; adjusted P = .656) for fevipiprant 450 mg versus placebo. There was no meaningful difference in the secondary end points for fevipiprant versus placebo. CONCLUSIONS: THUNDER provided no evidence of a role for fevipiprant in the treatment of patients with CRSwNP and asthma; future studies may establish a role for other DP2 antagonists, specifically in patients with aspirin-exacerbated respiratory disease.

Odours count: human olfactory ecology appears to be helpful in the improvement of the sense of smell.

Odours modify human behaviour. Research in this field develops rapidly, providing more and more exciting discoveries. In this context, our daily odorous environment has been surprisingly poorly explored. The aim of our study was to quantify olfactory perception and preliminarily identify factors affecting the frequency of odorous experiences. We were also interested in knowing whether human olfactory ecology relates with olfactory performance. In this study, patients with olfactory deficits (n = 62) and healthy controls (n = 97) had their olfactory threshold and odour identification abilities measured before and after a two-week intervention comprising counting of conscious perception of odours naturally occurring in the environment. In both groups, we observed enhanced olfactory performance after the intervention suggesting that (1) the conscious focus on odours may change its perception, and that (2) social and physical environment can effectively stimulate the human olfactory system, presumably supporting the improvement of olfactory sensitivity.

Emergency Treatment of Anaphylactic Reactions in Air Rescue Missions: An Eight-Year Analysis of a German Rescue Helicopter Base.

INTRODUCTION: Anaphylactic reactions can lead to a life-threatening situation. In the event of anaphylaxis, rapid and targeted emergency treatment is indicated. STUDY OBJECTIVE: The study sought to determine the emergency therapy administered for anaphylaxis in children and adults. Focus was placed on therapy with adrenaline. In addition, the study aimed to investigate demographic data, triggers, and hospitalization rates of the different severities of anaphylaxis. METHODS: A retrospective analysis of anaphylactic reactions was conducted using data from prehospital emergency missions performed by the Air Rescue Dresden/Germany from 2008 through 2015 using the standardized application protocol EPRO-5.0 (MIND 3) anonymized. Data from 152 adults and 29 children were evaluated, focusing especially on the acute treatment as well as demographic information, triggers, and symptoms of anaphylactic reactions. RESULTS: In total, 152 adults (73 female, 79 male) from 18 to 87 years (mean 50.5 years) and 29 children (9 female, 20 male) from 1 to 16 years (mean 7.5 years) with anaphylactic reactions were analyzed. The most common trigger for severe anaphylactic reactions (Grade II-IV; classification modified according to Ring and Messmer) was food in children (33%) and insect venom in adults (59%). The data show that 19% of adults with Grade II-IV anaphylactic reactions (classification modified according to Ring and Messmer) received adrenaline. Regarding children, the appliance of adrenaline was only administered in seven percent of the cases of Grade II-IV anaphylactic reactions. Adults with Grade II or higher anaphylactic reactions were hospitalized in 92%. Three percent refused hospitalization and five percent were not transferred to hospital. One-hundred percent of the children with Grade II-IV anaphylaxis were hospitalized. CONCLUSIONS: Analysis of data from the Air Rescue Dresden/Germany shows that despite existing recommendations, only 19% of adults with severe anaphylaxis received adrenaline. Among children, only in seven percent was a treatment with adrenaline performed.On the other hand, all patients survived the acute emergency treatment without apparent adverse outcomes. Thus, further studies are needed to determine the proper use of adrenaline in anaphylactic reactions.

Symptoms of Depression in Patients with Chemosensory Disorders.

INTRODUCTION: Patients with chemosensory dysfunction frequently report symptoms of depression. The current study aims to clarify whether the type (smell dysfunction, taste dysfunction, and mixed smell and taste dysfunction), severity, duration, or cause of dysfunction have differential impacts on the symptoms of depression. METHODS: 899 patients with chemosensory disorders and 62 controls were included. Following a structured interview and an otorhinolaryngological examination, subjects underwent olfactory tests (Sniffin' Sticks), gustatory tests (taste sprays) and an assessment of depressive symptoms (Beck Depression Inventory). Information on the cause and duration of disorders was also collected. RESULTS: Patients with combined olfactory/gustatory dysfunction had higher depression scores than patients with smell dysfunction only and controls, and no significant difference was found between the smell dysfunction and controls. Anosmia patients, but not hyposmia patients, exhibited higher depression scores than controls. Among various causes of chemosensory disorders, patients from the posttraumatic group had higher depression scores than patients with other causes of chemosensory dysfunction (sinonasal, idiopathic, or postinfectious). Multiple linear regression analyses suggested that reduced olfactory function was associated with enhanced depression scores in the olfactory disorders group (B = -0.326, t = -2.294, and p = 0.02) and in all patients with chemosensory disorders (B = -0.374, t = -2.550, p = 0.017). DISCUSSION/CONCLUSION: Simultaneously decreased input of olfaction and gustation seems to have an additive effect on the exacerbation of emotional dysfunction. Early intervention should be considered for depression symptoms in patients with mixed olfactory/gustatory dysfunction in clinical practice.

[Biologics: A New Option in Treatment of Severe Chronic Rhinosinusits with Nasal Polyps]. / Biologika: Neue Therapieoption bei schwerer chronisch polypöser Rhinosinusitis.

Chronic rhinosinusitis (CRS) is defined as an inflammation of the nose and paranasal sinuses with prevalence of 10.9 % and by the presents of 2 or more symptoms, which last more than 12 weeks. The symptoms are nasal obstruction, nasal discharge (anterior/post nasal drip), facial pain or pressure and/or olfactory disorder. CRS has a high negative impact on an individual's quality of life. The pathogenesis is multifactorial and complex. CRS has been subclassified into 2 groups: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Regarding further knowledge of the inflammatory pathway the primary CRS is considered by endotype dominance, either type 2 or non-type 2. 80 % of the CRSwNP reveals a type 2 inflammation. The proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in nasal polyp tissues pattern. CRSwNP is often refractory to medical and surgical management, especially in patients with asthma and aspirin intolerance. In most cases the control of the disease is a challenge. Patients with asthma but especially with Samter's triad are significantly more likely to have a recurrence of nasal polyps and undergo a second surgery following recurrence. In patients with severe CRSwNP, in whom the current standard of care including topical and oral corticosteroids, antibiotics and surgical procedures fail to control the disease, biologics can open new perspectives in treatment. They allow avoiding the possible adverse events resulting from repeated use of systemic corticosteroids and surgery. These biologics have a high impact on type 2 immune reaction and lead to a reduction of IgE as well as of local mucosal eosinophil migration and activation, resulting in a significant effect on nasal polyps, smell, quality of life and asthma comorbidity.