Per L. Larsen

Efficacy of an aqueous and a powder formulation of nasal budesonide compared in patients with nasal polyps.

Nasal polyps are commonly treated surgically. Intranasal administration of topical corticosteroids has gained increased acceptance as a treatment alternative. The aim of our study was to compare the efficacy of treatment of two formulations of budesonide with placebo on nasal polyps. At four Danish clinics 138 patients suffering from moderate or severe nasal polyps were randomized to a twice daily treatment with Rhinocort® Aqua 128 μg, Rhinocort Turbuhaler® 140 μg or placebo (Astra Draco, Sweden) for 6 weeks. Polyp size (primary efficacy variable), nasal symptoms, sense of smell, and patients’ overall evaluation of treatment of efficacy were assessed by scores. Polyp size was reduced significantly in both budesonide treated groups compared with placebo, but there was no statistical difference between the two actively treated groups. Patients’ nasal symptom scores was significantly more reduced in the Aqua compared to the Turbuhaler treated group, and both reduced symptom scores were significantly better compared to placebo. Sense of smell was significantly improved in the actively treated groups compared to placebo. The proportion of patients rating substantial or total control over symptoms after 6 weeks treatment was 60.9% and 48.2% in the Aqua and Turbuhaler-treated groups, respectively, which was significantly better compared with 29.8% in the placebo-treated group. Rhinocort Aqua and Rhinocort Turbuhaler were equally well tolerated.

Origin of nasal polyps

The nasoethmoid complexes from 6 patients with nasal polyps were systematically examined. First, the location and place of the origin of the polyps were recorded and photographed. The polyps and their places of origin were removed, serial sectioned, and examined. In all 6 patients, the polyps originated from the nasal mucosa. Most of the polyps extended laterally from the mucosa into the anterior part of the middle meatus. Several polyps originated from the mucosa near the ethmoid cell ostium or directly from the mucosa lining the edge of the ostium. The ostia themselves were not blocked by the polyps, and there was no indication of polyp formation in the ethmoid cells.

Experimental Long-term Tubal Occlusion in Cats: A Quantitative Histopathological Study

Unilateral tubal occlusion was performed in 10 cats, which were sacrificed 26-44 months later. During the observation period repeated bilateral tympanometry and auditory nerve response were recorded. Paracentesis with evacuation of effusion was performed up to eight times and the effusion was examined by viscometry. After sacrifice, quantitative histopathology of the bulla with determination of goblet cell density was carried out. In three ears having glue at the last paracentesis, the histopathologic changes were more pronounced than in the four ears having thin effusion. Three ears were dry at sacrifice with normal tympanometry, the histopathological changes evidently demonstrate the the normalization of the middle ear mucosa. The experiments demonstrate the great importance of tubal patency or function in prognosis of the disease. In ears with anatomically occluded tubes, no recovery occurred, whereas in ears with normalized tubal function, the middle ear mucosa and goblet cell density also normalized. Pathogenic and etiological aspects of secretory otitis are discussed.

Nasal polyps: epithelium and goblet cell density.

The density of goblet cells was determined in 14 anterior and 15 posterior nasal polyps using the whole‐mount method. The specimens were then serial cut and the type of epithelium was determined in nine localities in each polyp. The goblet cell density was correlated to the epithelial type. Pseudostratified, cylindrical epithelium was the prevailing type, occurring in 62% of anterior localities and 78% of posterior localities. Transitional types of epithelium were found in 33% of the anterior and 19% of the posterior localities. Stratified squamous epithelium occurred in 5% and 3%, respectively. The goblet cell density was highest in hyperplastic pseudostratified epithelium, whereas it was four times lower in transitional epithelium and even lower in squamous epithelium. Marked differences in the distribution of epithelium and goblet cell density were found between anterior and posterior polyps, illustrating that the epithelium constantly changes under the influence of air current, contact with other polyps, infection, growth, and age of the polyp as well as other unknown factors.

Topical budesonide treatment reduces endothelial expression of intercellular adhesion molecules (vascular cell adhesion molecule-1 and P-selectin) and eosinophil infiltration in nasal polyps

Infiltration of eosinophil granulocytes and endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and P-selectin was investigated in biopsies of polyps and inferior turbinates from 16 patients with nasal polyps, by the use of immunohistochemical staining and stereological quantification before, during and after topical treatment with budesonide (Rhinocort Turbuhaler). Before glucocorticoid treatment a higher density of eosinophil profiles (p < 0.005), making up a larger proportion of the total cellular infiltrate (p < 0.0005), was found in the polyps compared with the inferior turbinates. Endothelial VCAM-1 expression was higher in polyps than in inferior turbinates (p < 0.005), in contrast with the expression of P-selectin, which was more frequently expressed in the inferior turbinates (p < 0.05). Topical glucocorticoid treatment reduced the density of eosinophil profiles (p < 0.05) and the endothelial expression of VCAM-1 (p < 0.007) and P-selectin (p < 0.02) in polyps. Eosinophil counts and VCAM-1 expression returned to pre-treatment levels 8 weeks after discontinuation of budesonide treatment. The observed reduction in endothelial expression of cellular adhesion molecules may interfere with cellular recruitment in nasal polyps and thus contribute to the known anti-inflammatory effect of glucocorticoid in nasal polyposis.

Nasal polyps and their relation to polyps/hypertrophic polypoid mucosa in the paranasal sinuses: a macro-, endo-, and microscopic study of autopsy materials.

The present study comprised macro- and endoscopic screening of the nasosinusal complex in 56 autopsies, 24 with nasal polyps and 32 without. Seven had nasal polyposis (bilaterally more than two). Hypertrophic polypoid mucosa in the paranasal sinuses was not found in the cases with nasal polyposis and in only 2 (4%) of the total number (24) of cases with polyps. Microscopic examination of nine small polyps, the mucosa from which they originated, and control specimens showed accumulation of eosinophils in the mucosa from which the polyps originated, indicating localized inflammation.

Goblet Cell Density in Nasal Polyps

The goblet cell density was determined in 29 nasal polyps from 22 patients by use of the periodic acid Schiff-alcian blue whole-mount method. The distribution of goblet cells was found to be extremely irregular, ranging from areas completely devoid of goblet cells to areas with a relatively high density. The median density varied from 280 cells/mm2 to 10,000 cells/mm2. The total median density for all 15 polyps located anteriorly in the nose was 3,450 cells/mm2, compared with 6,050 cells/mm2 for 14 posteriorly located polyps. The density was highest in pseudostratified, cylindric epithelium, although great variations occurred among the different areas with this type of epithelium. The goblet cell density may be influenced by several factors, such as the airflow, type and thickness of the epithelium, and whether the genesis of the nasal polyps is infectious or allergic, in addition to polyp growth, size, and age.

Polyp Formation by Experimental Tubal Occlusion in the Rat

The purpose of this study was to show the early stages of polyp formation, as part of our studies on the pathogenesis of nasal polyps. Two and 4 weeks after experimental tubal occlusion in 18 Wistar rats, 13 showed signs of bacterial infection, respective acute otitis media. In the majority of these rats polypouslike protrusions of the middle ear mucosa were found in whole-mount specimens. All polypouslike protrusions were investigated by cross sections, which revealed localised accumulation of fluid and inflammatory cells in the lamina propria. The polyps were covered with a flattened epithelium, compared to the epithelium in the surroundings. In some of the bigger polyps the apical part was without epithelial covering. The findings suggest that the epithelium by fast polyp growth may be distended and may burst, or that a primary epithelial defect has not been sufficiently covered.

Pathogenesis and Pathophysiology of Nasal Polyps

The pathogenesis of nasal polyps explains how the polyps start and grow. The pathophysiology of nasal polyps explains the events and processes taking place in the outgrowth of nasal polyps. Histopathological studies at various stages of polyp formation, using whole-mount methods, the glands of the uncut polyps and the ordinary histological sections, allow our statements on pathogenesis of nasal polyps. Origin and incidence of nasal polyps on autopsies, studies on the changing epithelium and quantitative studies of the inflammatory cells of the nasal polyps, removed from the patients, allow us some statements on pathophysiology of the nasal polyps. In fact, only the age of the nasal polyps separates the term pathogenesis from the pathophysiology.

Early Stages in the Development of Goblet Cells in the Paranasal Sinuses: A Multimethodological Study in the Rabbit

To evaluate the pattern of goblet cell differentiation in sinus mucosa in response to external stimuli, New Zealand White rabbits were subjected to either experimental sinusitis or topical capsalcin application. Sinus mucosa was examined by light microscopy after serial sectioning, whole-mount preparation or immunohistochemistry. The mucosa was also examined by electron microscopy after perfusion fixation or high-pressure freezing. While goblet cells were normally very scarce in the healthy rabbit maxillary sinus mucosa, such cells were frequent after experimental sinusitis or topical capsaicin application. The process of goblet cell differentiation seems to follow a sequential path where serous secretory cells start to produce an increasing amount of mucous granules which appear electron lucent after conventional fixation. Parallel to this shift in secretion production, the cell assumes a bulging appearance after conventional fixation. It is concluded that newly formed goblet cells are recruited from intermediate secretory cell stages rather than from ciliated cells.