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.

Nasal polyp load determines the recovery of olfaction after surgery for chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is typically accompanied by impairment of olfaction. Despite of this, until today the efficacy of endonasal sinus surgery (ESS) in terms of olfactory function is still unclear. So far it is known that patients with nasal polyps are most likely to experience post-operative recovery. Within the present study we investigated the sense of smell and other parameters of impairment in CRS before and after ESS in relation to the degree of nasal polyposis, determined with the nasal endoscopic Lildholdt-score. METHODS: Patients with different degrees of severity of nasal polyposis were included. Olfactory function was assessed for odor thresholds [T], odor discrimination [D] and odor identification [I] and the changes of these parameters were investigated postoperatively. RESULTS: For 72 patients baseline measures were available and in 47 patients, postoperative changes were described. There was a correlation between olfactory scores and nasal anatomy/polyposis scores (Lildholdt scores, Lund-Mackay CT score), rated nasal health, and nasal quality of life (sinonasal outcome test). Three months after surgery the average TDI-Score improved by 3.1 points with 30% of patients showing significant clinical improvement. Patients with severe polyposis (Lildholdt score of 5 or 6) benefited most in terms of olfaction. Other significant prognostic indicators of a postoperative increase of olfactory scores included younger age, low pre-operative TDI-scores and high CT-scores. CONCLUSIONS: This study shows that not only the presence of polyps in CRS, but also the degree of nasal polyposis - measured by a grading system - predicts the results in olfactory test results. Additionally, the degree of recovery of olfaction after ESS seems to be most relevant in patients with high polyp scores.

[Relevance of nasal provocation testing in house dust mite allergy]. / Stellenwert der nasalen Provokation bei Hausstaubmilbenallergie.

Patients with house dust mite allergies frequently exhibit very different symptoms to those allergic to other inhalant allergens. The frequency of comorbid allergic asthma in these patients is increased. Therefore, diagnosing patients with suspected house dust mite allergies can be difficult. It is important to distinguish between sensitization to an allergen and a clinically relevant allergy. Nasal provocation testing (NPT) is a reliable method to identify patients suitable for a causal treatment (specific immunotherapy). Position papers on methodology and interpretation of NPT data are available. Skin prick and allergen-specific IgE tests reveal a reasonable correlation with NPT results, although this is inexact to some extent. Performance of NPT in patients with suspected house dust mite allergy is important in individuals with questionable symptoms and unclear skin and blood test results, particularly prior to initiation of allergen immunotherapy.

[Impact of Microsurgical Exstirpation of Vestibular Schwannomas on the Sense of Taste]. / Effekt der mikrochirurgischen Entfernung von Vestibularisschwannomen auf das Schmeckvermögen.

Patients with single sided vestibular schwannoma may report about a taste dysfunction apart from the well known cardinal symptoms. Very few data are published so far on that topic. The aim of this study was to investigate the influence of microsurgery for vestibular schwannomas on taste perception prospectively using a well validated taste test. 25 patients could be included in the study. No ageusia was claimed by the patients. In average a decrease of the taste score postoperatively could be detected on the tumor as well as on the non treated side. The differences were not statistically significant. But a subgroup of » of the subjects revealed a new onset of side difference in the taste score that was not present before surgery. In all those cases the treated side showed a clinically significant reduced taste score of 6,2 in average. Within this subgroup the temporal access was overpresented in contrast to the whole group. This may indicate an influence of the choosen approach and that for the position of the tumor to the change of the taste score. The observations should be verified on a greater collective.

Comparison of subjective olfaction ratings in patients with and without olfactory disorders.

OBJECTIVE: Olfactory dysfunction is common. The reliability of self-assessment tools for smell testing is still controversial. This study aimed to provide new data about the accuracy of olfactory self-assessment compared with a standardised smell test. DESIGN: Prospective, controlled, cohort study of patients with olfactory disorders and healthy controls. SUBJECTS: Ninety-six patients with a smell deficit and 71 controls were asked to rate their sense of smell on a visual analogue scale. Their olfactory abilities were also evaluated with the Sniffin' Sticks tests. RESULTS: The whole cohort showed a significant correlation between visual analogue scale smell scores and Sniffin' Sticks total scores. This correlation was also significant in the patient group, but not in the control group. These results were independent of olfactory deficit aetiology and subject age. CONCLUSION: Self-assessment of olfaction is only a reliable indicator in smell-impaired patients, not in healthy controls. For an accurate assessment of olfaction, reliable, standardised tests are needed.

[Deficits in medical counseling in olfactory dysfunction]. / Defizite der ärztlichen Beratung bei Riechstörungen.

Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

Evaluation of the efficacy of the 'nasal airflow-inducing manoeuvre' for smell rehabilitation in laryngectomees by means of the Sniffin' Sticks test.

OBJECTIVE: To determine the efficacy of the nasal airflow-inducing manoeuvre (NAIM) as a method for olfactory rehabilitation in laryngectomees by the means of the Sniffin' Sticks test. STUDY DESIGN: Prospective open interventional trial. SETTING: Tertiary academic hospital. PARTICIPANTS: Thirty-seven patients after laryngectomy have been screened and 25 patients have been included into the study. The participant's sense of smell was tested with the Sniffin' Sticks test before and after learning the nasal airflow inducing manoeuvre. The individual level of threshold, discrimination and identification (TDI) was determined and the individual threshold, discrimination and identification score was used to classify the patients as being anosmic, hyposmic or normosmic. MAIN OUTCOME MEASURES: The primary endpoint was the change of the threshold, discrimination and identification score before and after learning the nasal airflow inducing manoeuvre. The secondary endpoint was a change in the diagnostic group (normosmic, hyposmic and anosmic) after learning of the nasal airflow inducing manoeuvre. RESULTS: There was a statistically significant increase in the total threshold, discrimination and identification score (P < 0.001) and the three sub-scores (P ≤ 0.02) before and after the learning of the nasal airflow inducing manoeuvre. Patients gained seven points on average in the threshold, discrimination and identification score. Twenty of 25 patients showed an increase of five or more point in the threshold, discrimination and identification score. In the classification of the smell ability, 15 of 25 patients showed a change to a higher class (hyposmic to normosmic or from anosmic to hyposmic or normosmic). CONCLUSION: The nasal airflow inducing manoeuvre is a method for the successful rehabilitation of the sense of smell in laryngectomees. The evaluation with the Sniffin' Sticks tests showed a clinically relevant increase of olfaction in 80% of patients. The teaching of the nasal airflow inducing manoeuvre should be included in post-laryngectomy rehabilitation programmes.

[Cogan's syndrome: a diagnostic challenge]. / Das Cogan-Syndrom: Eine diagnostische Herausforderung.

Classical Cogan's syndrome is a disease of the inner ear with participation of the eyes, typically involving keratitis. If no objectively assessable optical symptoms are present, a diagnosis is difficult. Additional nonspecific symptoms can, combined with inner ear participation, suggest Cogan's syndrome. Between 2001 and 2003, we documented the course of two patients with Cogan's syndrome. As indicated in the literature, organ related symptoms could be related to a generalized vascular illness. In addition to the usual otological symptoms with cochleovestibular dysfunction and symptoms of typical and atypical ocular manifestations, other non-specific changes were found. Interstitial keratitis was diagnosed in one patient while in the second objective ophthalmological symptoms failed. The symptoms could be improved by systemic and local administration of corticosteroids and immunosuppressive therapy, however, progression of inner ear deafness could not be stopped in one patient and a cochlear implant was necessary.

[Studies of the olfactory epithelium in anosmic patients after head trauma]. / Untersuchungen der Riechschleimhaut von anosmischen Patienten nach Schädel-Hirn-Trauma.

BACKGROUND: An additional diagnostic option for olfactory dysfunction is the study of the olfactory epithelium. METHODS: Biopsies of the olfactory epithelium were performed under local anaesthesia on five patients with a history of head trauma with anosmic results in the Sniffin' Sticks test. The biopsy of a normosmic patient served as a control. Immunochemistry of frozen sections and explant culture studies were made, investigating ability to attach to the culture plate and the outgrowth of neuronal cells after growth-factor stimulation. RESULTS: The biopsies were carried out without any complications. All biopsies were positive for neurofilament, a marker for immature neurons. Substantial differences in the explants' ability to attach to the culture plate occurred, with a rate of between 25% and 100%. The control showed 67%. After stimulation with growth factors (FGF(2)), the cultures with more attached cells showed neuronal differentiation with the appearance of bipolar cells. CONCLUSIONS: The biopsy of the human olfactory epithelium is a minimally invasive procedure which can provide further information on specific changes and possible regenerative ability. Further studies with larger numbers of patients with different causes of an impaired sense of smell are needed to determine specific changes.

[Myospherulosis of the middle ear -- a rare differential diagnosis of cholesteatoma]. / Myospherulose des Mittelohres -- eine seltene Differenzialdiagnose des Cholesteatoms.

BACKGROUND: Myospherulosis is a chronic-inflammatory lesion that is most commonly iatrogenic of origin and occurs in tissues exposed to petrolatum-based products. The disease does not exhibit characteristic symptoms and is therefore not diagnosed in some instances. In previous otorhinolaryngological studies, myospherulosis was mainly found in paranasal sinuses, while only four otitic cases have been reported. METHODS: A 48-year-old female Egyptian patient suffered from bilateral chronic otitis media that had been treated in Egypt by tympanoplasty. The patient presented few months later at the university ENT department (Mainz) with deteriorated otorrhea and otalgia. Clinical, otoscopical, and radiological examination led to the diagnosis of cholesteatoma. During revision surgery of the right side, ointment-like material was found, which was embedded in granulation tissue. Middle ear biopsies were taken from both sides and routinely processed for standard histological examination and transmission electron microscopy. RESULTS: Histological examination of the right middle ear biopsy showed cystic tissue spaces lined by histiocytes and foreign-body giant cells in a fibrous stroma. In the tissue spaces, scattered debris and sac-like structures containing round spherules of aggregated erythrocytes were found. In addition, erosion of adjacent bone matrix was seen. Diagnosis of myospherulosis was made. By contrast, histological evaluation of the left middle ear biopsy revealed cholesterol granuloma. CONCLUSION: Myospherulosis of the middle ear has been hitherto diagnosed in a very few otitic cases, but might be overlooked as it mimicks other chronic proliferative and inflammatory lesions such as cholesteatoma in the present case. Thus myospherulosis should be considered in otitic cases with a suspicious history (exposure to petrolatum-based products). Furthermore, patients with myospherulosis have a significantly higher likelihood of developing postoperative complications. Since the lesion exhibits distinct histological findings, microscopy plays a central role for the diagnosis of this important disease.

Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.

Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and viewed in slow motion to count the frequency. PGE2 led to a dose-dependent increase in CBF. This became significant at concentrations of 10(-10) and 10(-5) M (P < 0.01) but not at 10(-13) M (P > 0.05). Addition of cAMP (10(-10) to 10(-5) M) caused a significant (P < 0.01) increase in CBF, whereas depletion of endogenous cAMP after pre-incubation with the adenylate cyclase activator forskolin (10(-5) M) prevented the PGE2-induced increase in CBF (P > 0.05). The ciliostimulatory effect of PGE2 depends on an intact functioning of adenylate cyclase. These results point out that cAMP is directly implicated in the signal transduction pathway of PGE2-induced stimulation of CBF in cultured human ciliated cells of the nasal mucosa.