Boris R. Haxel

Olfactory training is helpful in postinfectious olfactory loss: A randomized, controlled, multicenter study

The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent postinfectious olfactory dysfunction (PIOD).

Confocal endomicroscopy: a novel application for imaging of oral and oropharyngeal mucosa in human

Confocal endomicroscopy is an emerging technique for intravital visualization of neoplastic lesions, but its use has so far been limited to the gastrointestinal (GI) tract. This study was designed to assess the feasibility of in vivo confocal endomicroscopy of different regions of the oropharyngeal mucosa and to evaluate different contrast agents. We examined five different regions of the human oropharynx in vivo, and images were collected in real time by using a confocal laser endoscope as formerly described for the GI tract. Additionally ex vivo specimens were examined using a topical contrast agent. Confocal scanning was performed at 488-nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). Confocal endomicroscopy allowed for visualization of cellular and subcellular structures of the anterior human oropharyngeal region. Fluorescein staining yielded architectural details of the surface epithelium and also subepithelial layers. Images taken at increasing depth beneath the epithelium showed the mucosal capillary network. Acriflavine strongly contrasted the cell nuclei of the surface epithelium. The findings correlated well with the histology of biopsy specimens. This is the first report showing that the use of fluorescence confocal endomicroscopy represents a promising method to examine cellular details in vivo in different oropharyngeal regions in human.

Objective Assessment of Terbinafine-Induced Taste Loss†

Objectives: Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so‐called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole‐mouth testing of a single subject, found no terbinafine‐related deficit. In this study, we quantitatively assessed, using well‐validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age‐, race‐, and sex‐matched normal controls.

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

Abstract 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.

Controlled trial for long-term low-dose erythromycin after sinus surgery for chronic rhinosinusitis

The efficacy of macrolides in chronic rhinosinusitis (CRS) is still under controversy. To date, only two double‐blind, placebo‐controlled studies have been published with differing results. None of these studies investigated the possible benefit of macrolides in the postoperative period. We conducted an investigator‐initiated clinical trial using 250‐mg erythromycin once a day over a period of 3 months, beginning the administration of either erythromycin or placebo 2 weeks after a surgical intervention for CRS.

Evaluation of the efficacy of the ‘nasal airflow-inducing manoeuvre’ for smell rehabilitation in laryngectomees by means of the Sniffin′ Sticks test

Clin. Otolaryngol. 2011, 36, 17–23

Correlation of Skin Test Results and Specific Immunoglobulin E Blood Levels with Nasal Provocation Testing for House-Dust Mite Allergies:

Background Allergen-specific immunotherapy for house-dust mite (HDM) allergies is associated with lower success rates when compared with similar treatments for other inhalant allergens, such as grass or birch. One reason might be the greater difficulty in diagnosing patients with assumed HDM allergies because symptoms occur perennially and may differ from those of a conventional allergic rhinitis. Objective The aim of the study was to compare the different methods of diagnosis in patients with assumed HDM allergy. Methods We performed a retrospective analysis of nasal provocation tests (NPT) from patients (n = 161) evaluated for Dermatophagoides pteronyssinus (n = 127) and Dermatophagoides farinae (n = 104) allergies, and compared the results with other allergen testing methods (skin-prick test [SPT], intracutaneous test, and allergen specific immunoglobulin E levels [sIgE] to detect sensitization). Receiver operating characteristic curves were used for the analyses and the areas under the curve were calculated. Results For D. pteronyssinus and D. farinae, 86 and 70 complete data files, respectively, were available. For both tested HDMs, the results of the receiver operating characteristic curves showed a significant correlation for SPT and sIgE, with the results of the NPT (area under the curve, 0.742 to 0.763) but not for the intracutaneous test. In patients with a positive SPT (≤3 mm), an allergy was confirmed by the NPT in 69% of cases for D. pteronyssinus and 71% for D. farinae. A positive sIgE result (ImmunoCAP class of ≤2) was verified by the NPT in 69% of cases (D. pteronyssinus) and 70% (D. farinae). Conclusion The predictability value for a positive NPT result is best for SPT and sIgE. Nevertheless, even if the results of both test systems are combined, the positive predictive value that was achieved was only 0.77 for D. pteronyssinus and 0.69 for D. farinae. Therefore, in patients eligible for immunotherapy for HDM, an NPT should be performed before the start of the therapy to verify a clinically relevant allergy.

The Candy Smell Test in clinical routine.

Background The “Candy Smell Test” (CST) has been introduced as a new testing method for the evaluation of the human sense of smell. In contrast to other established orthonasal smell tests, the CST addresses the retronasal application of odors, typical for food aroma effects during mastication and swallowing. The aim of this study was to evaluate the CST in a clinical setting in patients with olfactory dysfunction and normal controls against the Sniffin’ Sticks test. Furthermore, cutoff points for normal and pathological results in the CST should be determined. Methods The olfactory performance of 96 patients presenting with olfactory disorders and 71 healthy controls was evaluated with the CST—comprised of 23 different aromatized smell candies and the extended Sniffin’ Sticks test (threshold, discrimination, and identification). The control group was gender matched but included also younger persons. Results The tested subjects could easily understand the procedures and were motivated to participate. The CST correlated well with the Sniffin’ Sticks for all tested subjects and for patients (n = 96) and controls (n = 71). The proposed cutoff value to differentiate normosmia from hyposmia in the CST was a score of <16 (i.e., 16 correctly identified odors) of 23. A score below 13 in the CST was the cutoff value for anosmia. Conclusion The CST is an easy-to-handle reliable tool to investigate retronasal olfaction suited for clinical determination of normosmia, hyposmia, and ansomia. In addition, it can be used for investigation where self-application is necessary such as in large survey studies.

Vascular Endothelial Growth Factor Expression in Nasal Polyps of Aspirin-Intolerant Patients

OBJECTIVE To study differences between aspirin-tolerant patients and aspirin-intolerant patients concerning vascular endothelial growth factor (VEGF) expression. Recent publications strongly suggest the involvement of VEGF and its receptors in the pathophysiologic process of nasal polyps. DESIGN We subjected 43 polyp specimens to semiquantitative immunohistochemical analysis. We quantified VEGF and its receptors (Flk, Flt, and neuropilin) in all samples. To gain insight into potential VEGF-mediated cellular responses, we determined proliferative (Ki67) and apoptotic (caspase 3) indices. PATIENTS Polyp samples were obtained from 22 aspirin-intolerant patients and from 21 aspirin-tolerant patients, and control specimens were obtained from 24 subjects with healthy nasal respiratory mucosa. SETTING Laboratory; Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. MAIN OUTCOME MEASURES Expression levels of VEGF, VEGF receptors. and proliferative and apoptotic indices. RESULTS We found higher expressed levels of VEGF and neuropilin and stronger proliferation in nasal polyps from aspirin-tolerant and aspirin-intolerant patients compared with controls. In polyps from aspirin-intolerant patients, VEGF was expressed at considerably higher levels compared with those from aspirin-tolerant subjects. Apoptotic activity remained unchanged in all 3 groups. CONCLUSIONS Nasal polyps from aspirin-tolerant and aspirin-intolerant patients are characterized by strong proliferation and high levels of VEGF and neuropilin expression. Nasal polyps from aspirin-intolerant patients show distinctly increased VEGF levels. The relevance of these findings for future therapeutic approaches is yet to be determined.

Dysregulated survivin expression in nasal polyps of individuals with aspirin exacerbated respiratory disease.

Background A derailed balance of cell proliferation and apoptosis is presumed to result in cell hyperplasia as a typical feature of nasal polyps. Survivin, a protein of the inhibitors of the apoptosis family is proposed to promote polyp formation. However, studies concerning survivin expression in chronic rhinosinusitis (CRS) with nasal polyps are rare and the specificity of the survivin expression in nasal polyps from individuals with aspirin-exacerbated respiratory disease (AERD) has not been investigated. Methods Immunohistochemical survivin expression analysis was performed. Samples were taken from the ethmoid sinus of individuals with CRS with nasal polyps with and without AERD during sinus surgery and control specimens of the inferior turbinate from individuals without CRS. Cell cultures were stimulated with recombinant vascular endothelial growth factor (VEGF165) and the resulting survivin expression was analyzed by Western blot. Results The survivin expression of 61 specimens was analyzed by quantitative immunohistochemistry d a potential VEGF-dependant stimulation of survivin in cell cultures was investigated. The survivin expression in nasal polyps from individuals with AERD was increased compared with the controls (median, 1194 versus 927 arbitrary units [A.U.]; p = 0.054). Western blot analysis revealed in vitro a VEGF-dependant regulation of survivin in nasal polyps from individuals without AERD, but not in those with AERD (p = 0.05). Conclusion Enhanced survivin expression might result in decreased apoptosis and cellular hyperplasia as a part of the largely unknown pathophysiology of nasal polyp formation. Furthermore, we hypothesize a pathological, VEGF-independent constitutive survivin expression in nasal polyps of individuals with AERD.