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Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa.

The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps ( n=11) and controls of human mucosa of the normal middle turbinates ( n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.

Endothelial Growth Factors↗

[Effects of corticosteroid on eosinophils and expression of transforming growth factor beta 1 in nasal polyps].

OBJECTIVE: To observe the effects of systemic steroids on the infiltration of eosinophils and the expression of TGF beta 1 in nasal polyps. METHOD: The SP immunohistochemical methods were applied to explore the expression of TGF beta 1 in nasal polyps before and after corticosteroids use; the optical density of positive cells in mucosal epithelia, eosinophils, glandular epithelium, vascular endothelial, matrix and mucous membrane was measured by using HPIAS-1,000 image-conduct system. RESULT: The expression of TGF beta 1 was positive in nasal polyps. The number of eosinophils and the expression of TGF beta 1 was significantly reduced in nasal polyps after treated with corticosteroids compared with pre-treated. CONCLUSION: The effects of systemical steroid use on the nasal polyps may depend on decreasing the infiltration of eosinophils and the expression of TGF beta 1.

Adult↗

Eosinophil infiltration is related to increased expression of vascular cell adhesion molecule-1 in nasal polyps.

Endothelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. Nasal polyps characteristically contain a leukocyte infiltrate in which eosinophils often are remarkably prominent. We have studied whether this feature is related to a particular profile of adhesion molecules on the local microvascular endothelium. Nasal polyps were obtained from 15 patients. Mucosal biopsy specimens of the lower and the middle turbinate from the same patients as well as from three control subjects served as reference tissue. Expression of endothelial adhesion molecules and the relative numbers of eosinophils and neutrophils were examined by two- and three-color immunofluorescence staining. Both the number of eosinophils and the proportion of vessels positive for vascular cell adhesion molecule-1 (VCAM-1) were significantly increased in nasal polyps compared with the turbinate mucosa of the same patients (P = 0.008 and P = 0.001, respectively). By contrast, the number of neutrophils and the relative expression of E-selectin and intercellular adhesion molecule-1 were similar at both tissue sites. Furthermore, the relative number of eosinophils in nasal polyps was well correlated (rs = 0.73, P = 0.006) with the percentage of vessels positive for VCAM-1, but this was not true for neutrophils. Taken together, this direct in situ observation strongly supports the crucial role suggested for VCAM-1 in human eosinophil extravasation at inflammatory sites.

Adult↗

Mucous glands in nasal polyps.

A total of 102 nasal polyps from 52 patients were stained by the PAS-alcian blue whole-mount method, and mucous glands were studied quantitatively. Glands were found in all polyps but in many of them only a few. The density is very low, considerably lower than in the nasal mucosa. The glands are tubular, of different shape and size, but differ widely from those in the nose and are formed from the surface epithelium after the polyp has attained a certain size. They do not issue from the nasal mucosa. The glands degenerate and distend. Thus, cysts in the polyp are degenerated, mucus-filled glands.

Adolescent↗

Incidence of medico-surgical treatment for nasal polyps on the development of associated asthma.

The surgical treatment of nasal polyps (in asthmatic patients) is still controversial today because of the contradictory, inconsistent, and unforeseen results reported in the literature. The 50 patients included in this study (mean age 49 years, range 25-67 years) came for a check-up on an average of 18 months (lower limit 12 months, upper limit 40 months) after a radical endoscopic intranasal ethmoidectomy. Thirty patients suffered from polyps and bronchial hyperreactivity; 12 patients in this group also suffered from aspirin intolerance. Twenty patients suffered from nasal polyps alone, and served as a control series. The following parameters were methodically noted relative to the date of ethmoidectomy: 1) the frequency of attacks and possible intervals of respiratory difficulty, pre- and postoperatively; 2) the basic treatment for the asthma, and the difference in size of the therapeutic doses necessary and/or the elimination of one or more therapeutic classes; 3) bronchospasticity, evaluated pre- and postoperatively by auscultation for wheezing and peak flow measurements. A bronchial challenge with carbamyl choline and a four-doses aspirin challenge over two days (10 mg, 50 mg, 100 mg, 400 mg) were carried out pre-and postoperatively in the absence of contra-indications. Ninety-one per cent of the patients have improved and now live in less discomfort. The factors studied show a lower frequency of attacks, a distinct decrease of respiratory difficulty, less need for anti-asthmatic medication and especially less oral corticoids, and a marked improvement in functional respiratory test. The carbamyl choline test confirms these data and even shows the totally reversible nature of nonspecific bronchial hyperreactivity in 30% of these patients. This series is too limited for us to say that intolerance to aspirin is reversible; perhaps only the reactivity threshold changes. In the 20 subjects with nasal polyps alone, no case of asthma have been recorded since the operation. Improvement of the asthmatic condition may be partly dependent upon a global diagnosis and treatment of the patient by the pneumo-immunoallergologist and the ENT-specialist. However, the nature of the surgical act seems to be of prime importance, and we must insist on the need for a radical marsupialization of the paranasal sinuses.

Aspirin↗

Role of allergy in nasal polyps of Thai patients.

As distinct from many countries, allergy in Thailand is of the perennial type which may play a role in the formation of nasal polyps. Forty consecutive patients with nasal polyps and 30 normal subjects as control were studied at the Allergy Clinic, Department of Otolaryngology, Pramongkutklao Hospital. A positive clinical history and skin allergy testing are diagnostic criteria for allergy. In the nasal polyps group, these were 28 males and 12 females, aged between 12-65 years, with an average age of 38.5 years. In the control group, there were 18 males and 12 females, aged between 15-53 yeas, with an average age of 34 years. All had received prick skin testing with 6 common aeroallergens. The prick skin test was considered positive when the wheal was > or = 3 mm with surrounding erythema. Twenty-four of 40 patients (60%) with nasal polyps had a positive prick skin test, while 6 in the 30 control cases (20%) had a positive prick skin test. This difference was statistically significant (P = 0.0019), Odd's ratio = 6.0 which means allergic persons were 6 times more prone to have polyps form than normal persons.

Adolescent↗

Albumin and immunoglobulin levels in nasal secretions of patients with nasal polyps treated with endoscopic sinus surgery and topical corticosteroids.

BACKGROUND: Nasal polyposis is principally treated by surgery, which may be combined with administration of topical corticosteroids to postpone or prevent recurrences. OBJECTIVE: In this study endoscopic sinus surgery and subsequent use of topical corticosteroids (budesonide) for 1 year was evaluated. METHODS: Clinical data of 41 patients with nasal polyps were evaluated, and their nasal secretions were compared with those of 26 healthy persons (control subjects). RESULTS: The patients had much higher initial total protein, albumin, IgM, secretory IgA (S-IgA) (p < 0.001 for all), and IgG concentrations (p < 0.05) than the control subjects. Treatment resulted in a significant decrease of S-IgA (p < 0.001) within 6 months. IgM and IgG concentrations decreased more slowly (p < 0.001 and p < 0.05 at 1 year, respectively). IgE levels decreased, but we could not demonstrate significance. Relative to total protein levels, the albumin and S-IgA levels decreased within 6 months (p < 0.005 and p < 0.001, respectively). The excretion of all proteins remained higher in patients than in the control subjects, even after 1 year of topical corticosteroid treatment. Clinical evaluation showed slightly higher S-IgA levels in patients with an IgE-mediated allergy than in those without such a condition, and the recurrence rate was highest in the former group (75% vs 48%). CONCLUSION: The data support the hypothesis that inflammatory reactions in the nasal mucosa play a role in the pathogenesis of nasal polyps but also suggest an additional causative factor.

Administration, Topical↗

A study of allergic factor in nasal polyp patients.

Various investigations for allergy were carried out on 57 nasal polyp patients. The majority of them (96.5%) showed positive responses to at least one of the methods used. The results suggest that allergy is a constant feature in the nasal polyp patients but that further investigation is needed before we can state that allergic manifestation contributes to polyp formation. It was also found in this study that 90% of the patients had definite pathological changes on their sinus x-rays. Sinus disease may be either predispose a patient to or result from nasal polyps.

Adolescent↗

[Effects of taking the pingzhi tablets on cellular infiltration in tissues of nasal polyps].

OBJECTIVE: To assess the effects of taking the "Pingzhi Tablets" on infiltration of inflammatory in tissues of chronic sinusitis and nasal polyps. METHOD: Nasal polyps from taking the "Pingzhi Tablets" treated patients (40 cases) and untreated patients (40 cases) were investigated. The samples were stained by HE and SABC-AP immunohistochemical methods. RESULT: Compared with untreated polyps, the polyps treated by taking the "Pingzhi Tablets" contained significantly lower tissue densities of CD 11b+, CD7+ positive cells. Although the densities of CD 19+ positive cells were lower in treated polyps, the differences were not statistically significant. CONCLUSION: The findings demonstrated tissue effects of treatment with taking "Pingzhi Tablets" and the treatment was effective in suppressing the inflammatory cell infiltration.

Adult↗

Nasal polyps: the relationship to allergy, sinonasal infection and histopathological type.

OBJECTIVE: To evaluate the relationship of nasal polyps to allergy, sinonasal infection and histopathological type by examining the prevalences of these factors among nasal polyps patients. STUDY DESIGN: Prospective descriptive study. MATERIAL AND METHOD: A total of 73 patients were enrolled between October 1st, 1999 and August 31st, 2002 at the Allergy and Rhinology Clinic, Faculty of Medicine, Songklanagarind Hospital. The medical history was recorded. Allergy skin prick test, nasal endoscopy with biopsy and plain film paranasal sinus were performed. Positive allergy skin test was defined by at least 1 aeroallergen with a wheal size > or = 3 mm greater than the negative control. Rhinosinusitis was diagnosed by clinical symptoms, positive nasal endoscopy and/or positive plain film paranasal sinus. Histopathological investigation was classified as eosinophil- or neutrophil-dominated inflammation. RESULTS: 68.5 per cent of patients with nasal polyps had a positive allergy skin test, 67.1 per cent had rhinosinusitis. Eosinophil-dominated inflammation was presented in 69.9 per cent and neutrophil-dominated inflammation in 30.1 per cent, respectively. Within each histopathological type, 62.7 per cent of patients with eosinophil-dominated inflammation and 81.8 per cent of patients with neutrophil-dominated inflammation had a positive allergy skin test. There was no statistically significant difference in prevalence of positive allergy skin test between eosinophil- and neutrophil-dominated inflammations (p = 0.107). 60.8 per cent of patients with eosinophil-dominated inflammation and 81.8 per cent of patients with neutrophil-dominated inflammation had rhinosinusitis. There was no statistically significant difference in prevalence of rhinosinusitis between eosinophil- and neutrophil-dominated inflammations (p = 0.079). CONCLUSION: Nasal polyps had association with positive allergy skin test (68.5%), rhinosinusitis (67.1%) and eosinophil-dominated inflammation (69.9%). There were no statistically significant differences in prevalence of positive allergy skin test and rhinosinusitis between eosinophil- and neutrophil-dominated inflammations (p = 0.107 and p = 0.079, respectively).

Adult↗

Histology of nasal polyps in various conditions.

At the Salata ENT Department in Zagreb, 28 patients with nasal polyps were examined in the 1992-1993 period. Results of histologic analysis of these nasal polyps are presented. In 10 cases, nasal polyps were histologically examined at three horizontal levels, and the rest by vertical section. The method of hemalaun eoisin and histochemical methods (PAS, Alcian, Mallory, Giemsa and orcein) were used to analyze the following parameters: epithelium, stroma, basement membrane, cell infiltrate and glands. Patients were grouped according to the presence or absence of allergy, relapse of polyps and age group ( < 40 and > 40 years of age). The lateral nasal wall mucosa served as control. Histologic picture of the polyps showed some differences related to allergy and other groups of polyposis. In conclusion, histologic study of polyps should not be taken as the only indicator of the etiology of polyposis but, supplemented with other examinations, as an evidence supporting the diagnosis.

Adolescent↗

Increased ion transport in cultured nasal polyp epithelial cells.

OBJECTIVE: To measure transepithelial bioelectric properties of cultured human nasal polyp and turbinate epithelial cells to test the hypothesis that nasal polyps have increased rates of ion transport. DESIGN: Cohort study. SETTING: Private referral center. PATIENTS: Individuals undergoing surgery for symptomatic nasal obstruction due to polyps caused by cystic fibrosis, nonatopic rhinosinusitis, or allergic rhinosinusitis. METHODS: Epithelial cells were removed from separated polyp and turbinate samples by protease disaggregation and cultured on permeable collagen matrix supports. Transepithelial potential difference and resistance were measured daily. At the time of maximal transepithelial potential difference, the cultures were mounted in modified Ussing chambers and exposed to a sodium-positive channel blocker (amiloride hydrochloride) and to selected chloride-negative channel agonists (isoproterenol bitartrate, adenosine triphosphate). OUTCOME MEASURES: Maximal transepithelial potential difference, resistance, and equivalent short-circuit current. Bioelectric responses to amiloride, isoproterenol, and adenosine triphosphate. RESULTS: Polyp cultures had higher transepithelial potential difference and equivalent short-circuit current than turbinate cultures. The mediator responses were greater for polyp than for turbinate cultures. CONCLUSIONS: Polyp epithelia have increased Na+ absorption and Cl- permeability relative to turbinate epithelia. These results are consistent with the hypothesis that increased epithelial fluid absorption contributes to the development of nasal polyps.

Absorption↗

The possible association of Chlamydia pneumoniae infection with nasal polyps.

The objective of this study was to investigate the possible etiologic role of Chlamydia pneumoniae infection in nasal polyps. This prospective clinical study was undertaken enrolling 30 patients with nasal polyps, and 30 age and sex-matched control subjects from whom epithelial material was obtained during endoscopic surgery. IgG specific ELISA was used to determine seropositivity, and indirect immunoflorescence to determine C. pneumoniae in the biopsy material. C. pneumoniae specific IgG antibodies were found to be positive in 16 (53.3%) of the patients with nasal polyps, and 9 (22%) of the control subjects (P = 0.065). Indirect immunofluorescence results indicate that there was a significant difference between groups; 16 (53.3%) patients in the study group and 8 (26.6%) patients in the control group were found to be positive (P = 0.034). We found no correlation with cigarette smoking. Our results indicated that Chlamydia pneumoniae is possibly associated with the presence of nasal polyps. However, these results remain to be confirmed with further studies using other techniques, and the underlying mechanism should be defined.

Adult↗

The nasal polyps as a tool for basic research in cystic fibrosis.

Total RNA and mRNA were prepared from cystic fibrosis (CF) and control nasal polyps and nasal epithelial cells. Genomic clones from the chromosomal region of the CF locus were screened by northern blots. A representative cDNA library from nasal polyps was cloned in the vector lambda gt10. For the construction of a physical genomic map around the CF locus single gene markers were isolated from metaphase 1:7q2qter chromosomes by laser micro-dissection and subsequent microcloning. A linkage study with the polymorphic markers met-H, met-D, and pJ3.11 was performed in 53 German CF families with at least 2 children. No significant correlation of any haplotype on the CF chromosomes with the clinical severity of the course of the disease could be observed, which provides evidence that cystic fibrosis is genetically homogeneous.

Chromosome Mapping↗

[Cytology of nasal polyps].

Cytograms were made from polyps and nasal mucosa in 30 patients suffering from chronic rhinitis and polyps. A semiquantitative method described in Otolaryngologia Polska in 1985 year was used. In 6 cytograms taken from polyps, neutrophils were found on an average in 93% of observed cells. In 24 cytograms the predominance of eozynophils was found on an average of 49%. In cytograms with predominance of eozynophils, basophils were found on an average of 13%. These results allowed the etiology to be distinguished and either pharmacological or surgical treatment to be applied, versus hitherto applied surgical treatment. In 6 eozynophilic patients cytograms were made from the mucosa 2 weeks after polypectomy. A considerable decrease or total disappearance of eozynophilic and basophilic cells was found.

Adult↗

Loss of secretory activity in the glands of nasal polyps.

Secretory activity in the glands of the nasal polyps from 15 patients with or without allergic histories was examined by using a direct (anti-IgA) or indirect (anti-SC) immunofluorescent technique. Glands were found in all the examined nasal polyps, but in many, only a few were present. Active secretory process of IgA was observed in the intraepithelial glands of the ciliated, pseudostratified epithelium. Most of the dilated glandular ductules, on the contrary, appeared to be lacking in secretory activity of IgA. Such were commonly filled with mucus materials and their epithelial glandular cells showed no fluorescence for anti-SC, whereas the active IgA secreting cells showed a heavy fluorescence for secretory component (SC) in indirect immunofluorescent studies. Activity of the glandular ductules, therefore, was determined by examining the SC producing activity. In some extracted polyps, SC containing dilated glands were present. These active glands, however, lost the SC producing activity followed by the stasis of mucus flow in the lumen. Thus, when the glands were occupied by mucus materials, stretched and cystic degeneration ensued.

Adolescent↗

Clinical and histopathological correlation of nasal polyps: are there any surprises?

Nasal polypectomy is a common operation. There is debate about whether all nasal polyps removed at operation should be sent for histopathological examination. To investigate this, a prospective study was performed to check the correlation of clinical and histopathological examination. Three hundred and forty-four nasal polypectomy specimens during the period from September 1997 to September 1999 were sent for histopathological diagnosis, with the clinical diagnosis documented on the pathology form. The clinical diagnosis was then correlated with the histological diagnosis. Three hundred and twenty-eight specimens were diagnosed as inflammatory polyps and 16 as tumours, of which seven were malignant. There was a good correlation between the clinical and histological findings in 340 cases. There was disagreement between the forms and reports in four cases. When the notes were consulted, three cases had forms that were incorrectly filled in. There was only one unsuspected case of inverted papilloma in a polyp specimen, which looked like a benign inflammatory polyp. This study indicates there is a 99.7% correlation between clinical and histopathological diagnosis.

Humans↗

[The secretion of chemokine RANTES in epithelial cells of nasal polyps and its significance].

OBJECTIVE: To investigate the effect of RANTES(regulated upon activation, normal T cell expressed and secreted) on chemotaxis, migration and accumulation of eosinophils in nasal polyps during epithelial immune responses. METHODS: The epithelial cells were obtained from nasal polyps and inferior turbinates in patients with snoring, and cultured for 24 and 48 hours with IL-1 beta(25 micrograms/L, 50 micrograms/L). RANTES was measured in the culture supernatant by ELISA. RESULTS: 1. On incubation with IL-1 beta, the epithelial cells from inferior turbinate and nasal polyps released 1.5-10 fold and 10-20 fold greater amounts of RANTES respectively than unstimulated samples. Significant increase in levels of RANTES was found in both groups(P < 0.001); 2. There was no difference between nasal polyp and inferior turbinate before incubation with IL-1 beta(P > 0.05) in the level of RANTES. After IL-1 beta stimulation, the concentration of RANTES was higher in polyp than in inferior turbinate (P < 0.001); 3. The expression of RANTES in both groups was dose-dependent and time-dependent upon stimulation of IL-1 beta. CONCLUSION: The epithelial cells of nasal mucosa are active end-organs, capable of releasing chemokine RANTES. In nasal polyps, RANTES has chemotactic activity for eosinophils and other inflammatory cells. It could affect the chemotaxis and eosinophil function and may play an important role in polyp formation.

Adult↗