Tomas Norlander

Experimentally induced polyps in the sinus mucosa : a structural analysis of the initial stages

To document polyp formation in the sinus mucosa, the authors of this study subjected New Zealand white rabbits to different modes of manipulation intended to induce inflammation of the maxillary sinus. These manipulations included a combination of bacterial infection and mechanical trauma, the deposition of agarose into the sinus cavity, and the deposition of N‐formyl‐methionyl‐leucyl‐phenylalanine, a chemotactic peptide, into the sinus cavity. A majority of animals developed polyps, which were examined by light and electron microscopy.

Experimental maxillary sinusitis induced by Bacteroides fragilis. A bacteriological and histological study in rabbits.

Experimental anaerobic maxillary sinusitis was induced in New Zealand White rabbits by blocking the ostium and inoculating Bacteroides fragilis, strain NCTC 9343. The animals were examined histologically and bacteriologically after 5 days, and 2, 3 and 4 weeks. All the infected sinuses displayed signs of moderate or severe inflammation throughout the study period. Ciliary damage and desquamation, hyperplasia and metaplasia of the epithelium were characteristic features. Furthermore, heavy leukocyte- and, particularly, round cell-infiltration, fibrosis, periosteal hyperplasia and bone degradation and -formation were also frequently encountered. The secretory cell count in the epithelium increased, including the regeneration of goblet cells. After 4 weeks no obvious recovery could be seen, and the inducing microorganism was re-isolated in the majority of cases. In comparison with experimental pneumococcal sinusitis, the B. fragilis infection exerts a more prolonged and severe inflammation.

Formation of Mucosal Polyps in the Nasal and Maxillary Sinus Cavities by Infection

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8. In another group of rabbits, sinusitis was induced by blocking of the sinus ostium only. Bacteriologic and light microscopic analysis was performed after 5 days to 1 month. Granulation-like polyps developed after deep mucosal inflammatory trauma initiating fibroblast proliferation, angiogenesis, and epithetlial migration to cover the polyp. In regions of a more superficial trauma—characterized by epithetlial desquamation and fibroblast growth—proliferation and differentiation of basal cells resulted in the formation of microcavities dissecting off edematous polyps. Polyps could be found in all sinusitis groups, irrespective of inducing agent. The cellular events of polyp formation appear to be the result of a continuous inflammatory reaction and are not directly related to the presence of a certain microorganism. Instead, the potential of any microorganism to induce a deep mucosal trauma or epithelial desquamation seems essential for its ability to initiate polyp formation. (OTOLARYNGOL HEAD NECK SURG 1993;109:522-9.)

The Inflammatory Response of the Sinus and Nasal Mucosa During Sinusitis: Implications for Research and Therapy

Since it is difficult to evaluate the state of an infected sinus mucosa by histopathology, much of the present knowledge of the morphology in sinusitis is based on animal experiments. When experimental sinusitis is induced in the rabbit, the inflammatory response in the nose appears to be more pronounced than that in the maxillary sinus. In the animal model, histological findings include epithelial desquamation, edema, goblet cell hyperplasia and, in severe cases, fibrosis, bone reaction and formation of polyps in the nose and in the antrum. These local pathological findings may persist in the nasal middle meatus and the paranasal sinuses for a considerable time and predispose the mucosa to recurrences of infection. By investigation with recently introduced advanced techniques such as magnetic resonance imaging (MRI), a protracted pathological state in the sinus mucosa can be recorded also in humans for months after an episode of acute sinusitis. Future human and experimental studies of the local inflammatory response and of the cellular pathology over time will yield further guidelines for improved therapy and prevention of acute sinusitis.

Mucosal Pathology of the Nose and Sinuses: A Study in Experimental Maxillary Sinusitis in Rabbits Induced by Streptococcus Pneumoniae, Bacteroides Fragilis, and Staphylococcus Aureus

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8 in order to study possible differences in the inflammatory response of the sinus and nasal mucosa at different time-intervals during a 12-week period of infection. The initial sinus mucosal response, most pronounced in pneumococcal sinusitis, was characterized by leukocytosis, epithelial desquamation, and squamous cell metaplasia. Tissue reactions at later intervals included fibrosis of lamina propria, gland involution, polyp formation, and bone remodelling, and were most pronounced in S. aureus and B. fragilis sinusitis. The nasal mucosa was altered with a redistribution of goblet cells, development of polyps in the ethmoidal region, involution of Bowmans glands and locally, areas of degenerated olfactory sensory epithelium. These findings endorse that the degree of local pathology depends on the infecting microorganisms specific pathogenetic factors. However, local tissue factors guiding the cellular inflammatory proliferative and regenerative processes are also of fundamental importance for the type of pathological changes occurring in an infected nasal or sinus mucosa.

The Relationship of Nasal Polyps, Infection, and Inflammation:

The role of infection as cause or effect in nasal polyps is debated. In experimentally induced sinusitis in rabbits, polyps are frequent. The initial polyp formation sequence involves multiple epithelial disruptions with proliferating granulation tissue. Regenerating epithelial branches spread into the underlying connective tissue, where intraepithelial microcavities give rise to a polyp body from the adjacent mucosa. Clinical as well as experimental studies indicate that nasal polyp formation and growth are activated and perpetuated by an integrated process of mucosal epithelium, matrix, and inflammatory cells, which in turn may be initiated by both infectious and noninfectious inflammation. The complexity of the pathophysiologic events in nasal polyposis is reinforced by the finding that epithelial desquamation, combined with infection or inflammation, will initiate polyp formation. Systemic glucocorticosteroids inhibit polyp formation as well as growth of pathogenic bacteria in the sinuses of rabbits with experimental infection. Therapeutic use of corticosteroids in polyp disease, combined with antibiotics or surgery, should be modified in relation to long-term progression, intensity variations, and predisposing conditions.

Expression of P-Glycoprotein 170 in Nasal Mucosa may be Increased with Topical Steroids:

The synthesis of P-glycoprotein 170 (P-gp), a “multidrug resistance” protein capable of extruding various drugs including 11-OH steroids from human cells, can be upregulated by certain glucocorticosteroids. This study demonstrates the presence of P-gp in the columnar surface epithelium and in glandular acini of healthy nasal mucosa with immunohistochemical technique. Furthermore, nasal polyps from 5 of 17 patients treated with clinical doses of a topical nasal steroid, budesonide, appear to show a stronger staining intensity for P-gp than polyps from 13 untreated patients. This suggests the possibility of local P-gp gene induction by topical glucocorticoid treatment. Upregulation of P-gp synthesis appears as a new possible cause of relative resistance to topical steroid medication in patients with nasal inflammatory disease.

Cellular Regeneration and Recovery of the Maxillary Sinus Mucosa: An Experimental Study in Rabbits

Unilateral maxillary sinusitis was induced in 30 New Zealand White rabbits with Streptococcus pneumoniae or Bacteroides fragilis. In another group of 15 rabbits without infection, the sinus mucosa was surgically removed in defined areas. In both series, the sinuses were serially sectioned for histological analysis of the cellular regenerative capacity. In maxillary sinusitis induced by Bacteroides fragilis, an inflammatory and also reparative process involving all mucosal layers including the underlying periosteum was seen. The more superficial trauma as found in pneumococcal sinusitis eventually led to restitution ad integrum. Following surgical removal, the denuded sinus-lining was reepithelized by a flattened ciliated epithelium on a lamina propria displaying fibrosis and lacking serous glands. The restoration of the rabbit maxillary sinus mucosa after surgical trauma thus leads to structural abnormalities of the epithelium as well as the lamina propria, and these changes are likely to interfere with the normal function of the sinus mucosa.

Current Perspectives on the Treatment of Nasal Polyposis: A Swedish Opinion Report

This Swedish study group has examined the current knowledge of nasal polyposis with emphasis on different treatment modalities. Polyposis is a multifactorial disease that exists for decades in the majority of cases. Different types of treatment must be considered, focusing on the underlying disease. However, as we only know the specific origin of polyposis in a minority of cases, treatment is usually symptomatic. When making a thorough evaluation of different treatment strategies, it is obvious that there is a real need for more controlled treatment studies which would make the scientific ground more stable when it comes to suggesting medical, surgical or combined treatments.

Effects of topical budesonide treatment on glucocorticoid receptor mRNA down-regulation and cytokine patterns in nasal polyps.

The effects of a topically applied corticosteroid, budesonide, on the expression of glucocorticoid receptor (CR) mRNA and regulation of pro-inflammatory cytokine patterns in patients with nasal polyps were evaluated. All patients were eligible for surgical polypectomy, and a majority of them had been treated with nasal steroids. Patients were given 400 μg b.i.d. (group A, n = 11), 200 μg bid. (group B, n = 10), or no treatment (group C, n = 15) during two months before polypectomy. Morning serum cortisol was analyzed on the day of surgery. Surgically removed polyps were taken for analysis of GR mRNA expression by solution hybridization. Remaining tissue was cryostat-sectioned, whereafter quantification of the cytokines interleukin 1β, interleukin 2, interleukin 4, interleukin 5, interleukin 6, interleukin 10, tumor necrosis factor a, and interferon γ was made by immunohistochemistry and digitized image analysis. No significant differences among the three groups were found for any of the parameters investigated. Conclusion: nasal polyps do not respond with down-regulation of CR mRNA or cytokines following topical corticosteroid treatment. The proposed corticosteroid resistance may be inherent, or induced by a change of local tissue bioavailability.