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.

Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease.

BACKGROUND: Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. METHODS: After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. RESULTS: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. CONCLUSION: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.

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.

The VEGF/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence.

BACKGROUND/AIMS: The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS. METHODS: A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation. RESULTS: All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors (p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213). CONCLUSION: Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.

No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis.

OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular protection against oxidative stress and reactive oxygen species. One major group of antioxidative active enzymes involved in cellular detoxification are the Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1 and variants of them are known, arising from allelic variations of the GST loci. Moreover, functional variants occur in high percentages and have been associated with diseases like bronchial asthma and bronchial hyperresponsiveness. The interplay of oxidative stress, detoxifying genes like GSTs and the genesis of respiratory tract illness is under contradictory debate. In this study, we analysed the potential association of GST-polymorphisms and chronic rhinosinusitis (CRS). METHODS: In total 170 nasal tissue samples, 49 tissue samples from patients with CRS without nasal polyps, 69 tissue samples from CRS with nasal polyps and 52 healthy tissue controls of the inferior turbinate were analysed for their individual GST-status. Genotypes for GSTM1 (null versus present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined by Polymerase Chain Reaction. The respective genotypes were correlated to the incidence of CRS with and without nasal polyps in aspirin-tolerant and intolerant patients and to the individual health status concerning asthma and allergies. RESULTS: No correlation between any GST-polymorphism and CRS with and without nasal polyps or allergies or asthma or aspirin-intolerance was observed. CONCLUSION: Our results do not suggest that there is a relevant genetic predisposition considering the individual GST-status for the susceptibility of nasal respiratory epithelia leading to CRS.

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.

[The value of ultrasound examinations, including intraoperative sonography, in ENT practice]. / Stellenwert der Ultraschalluntersuchung in der HNO einschliesslich intraoperativer Sonographie.

Sonography is an established part of routine ENT examinations. Due to the anatomy of the head neck region most organs and their diseases are easily accessible to sonography. Constant technical advances mean that ultrasound, due to its high resolution capabilities, represents an outstanding diagnostic alternative to magnetic resonance imaging and computer tomography. Sonography provides additional information of diagnostic value on various diseases occurring in the head and neck region. The use of sonography for diagnostic and follow-up examinations is integrated in daily clinical routine. Moreover, sonography is also a helpful intraoperative tool for both diagnostic and therapeutic reasons and offers new approaches for intraoperative navigation.

[Malignant thyroid neoplasms: a diagnostic challenge for ENT specialists]. / Das Schilddrüsenmalignom: Eine diagnostische Herausforderung für den HNO-Arzt.

BACKGROUND: Thyroid carcinoma is frequently diagnosed incidentally during routine ENT examinations. METHODS: Symptoms and clinical findings of 40 patients with thyroid malignancies presenting in our department were analysed retrospectively. The aim was to define characteristics indicative for the final diagnosis of thyroid malignancy. RESULTS: In 48% the initial presentation was not because of thyroid-specific complaints, however during the course of the general ENT examination, unspecific thyroid pathology was detected and further evaluated using sonography, scintigraphy and fine needle biopsy (FNB). The results of scintigraphy were suspicious in 67% and FNB was positive in 30%, inconclusive in 30% and false negative in 40%. For suspected malignancies a rapid frozen section examination was carried out which was positive only in 60% and false negative or inconclusive in 20% each. CONCLUSION: Thyroid lesions incidentally found during ENT examination should undergo ultrasound examination, FNB and scintigraphy with the clear understanding that there is no single diagnostic feature leading to the correct diagnosis and that only the synopsis of various findings and sometimes only final histology leads to the correct diagnosis.

Recurrence of a laryngeal spindle cell sarcoma with a transformation into a higher grade of malignancy.

Primary malignant mesenchymal neoplasms of the larynx are rare. Sarcomas of the larynx account for <1% of all malignant laryngeal mesenchymal neoplasms. This report examines a case of a recurring laryngeal, initial benign-appearing mesenchymal tumour, which first changed its clinical phenotype without any histological signs of malignancy and later also its histological appearance with signs of malignancy. Finally, it even underwent a transformation into a higher grade of malignancy. In addition to this, the difficulties of allocating this tumour to the correct sarcoma subentity are shown.