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Nasal polyps in children.

The inflammatory nasal polyp is the most common benign or malignant nasal mass seen in children. Nasal polyps in the pediatric population appear to occur as inflammatory responses to bacterial infections. In 33% of the patients with polyps whom we studied, antral choanal polyps were noted, and in 20% of the patients the polyps were unilateral but not antral choanal. In 18% of the patients the polyps were bilateral and in an additional 29% they occurred bilaterally in association with cystic fibrosis. History of an allergy is infrequently associated with nasal polyps; allergies are potentially major contributing factors to nasal polyps only in patients without cystic fibrosis whose nasal polyps are bilateral. Patients with antral choanal polyps are most successfully managed by simultaneous Caldwell-Luc antrostomy and polypectomy. Sixty percent of patients with nasal polyps and cystic fibrosis are adequately managed with a single intranasal polypectomy. Simultaneous sinus surgery and polypectomy should be considered for all patients with recurrent polyps and for all patients with clinical or radiographic evidence of significant sinusitis. Complications, including epistaxis and intranasal synechia, occurred in 3% of the 170 surgical procedures performed.

Adolescent↗

Distribution of the degranulated and non-degranulated mast cells in nasal polyp.

All of the nasal polyps obtained from 83 patients had mast cells which stained with toluidine blue in their tissue. Degranulated mast cells occurred much more in the deep stroma than in the part near the surface of the polyp. More degranulation of mast cells should have occurred in the superficial tissue than in the deep stroma if the inhaled allergen had reacted with specific IgE antibody on the mast cells in the polyp. The degranulation in the deep stroma in the nasal polyp means that another mechanism besides IgE-mediated degranulation must be operative in the mast cells. The pedicle of the nasal polyp had more mast cells and more degranulated ones than had the body and apex. Thus the pedicle is probably more important in the etiology of polyp formation in nasal mucosa than the body and apex from the viewpoint of the activity of histamine from degranulated mast cells on the blood vessels and nasal glands.

Cytoplasmic Granules↗

Nasal polyp inflammation. Effect of topical nasal steroid.

Topical nasal corticosteroid therapy produces clinical improvement in patients with nasal polyposis. To examine the mechanisms of steroid effect, we quantified the number of inflammatory cell types as well as the expression of relevant cell markers in nasal polyps from steroid treated patients (n = 11) and polyps from untreated patients (n = 10) judged to require polypectomy for symptomatic relief. We found that the majority of eosinophils in these tissues were in the stromal layers, and that the proportion of activated eosinophils (EG2+ versus total eosinophil count) was significantly lower in polyps from patients treated with the topical nasal steroid budesonide, 200 to 400 micrograms/d for 1 mo, than in polyps from untreated patients. We also found that in polyps from treated patients, the superficial stromal layer (SSL) and deep stromal layer (DSL) both contained a significantly lower tissue density of lymphocytes of CD3, CD4, and CD8 subsets. Treatment was also associated with a lower, albeit nonsignificant, expression of ICAM-1 and HLA-DR in the epithelium. The tissue density of CD14+ cells (monocyte/macrophage) and of tryptase+ cells (mast cells) was the same in the two groups. These findings demonstrate tissue effects of topical corticosteroid treatment which may point to the mechanisms of therapeutic benefit. In addition, these observations illustrate the value of markers that indicate cell functional activity rather than just cell numbers.

Administration, Intranasal↗

Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels. OBJECTIVES: Antagonizing the effect of IL-5 is a potential new treatment strategy in patients with nasal polyps. METHODS: In a double-blind, placebo-controlled, randomized, 2-center safety and pharmacokinetic study, 24 subjects with bilateral nasal polyps were randomized to receive a single intravenous infusion of reslizumab, a humanized anti-human IL-5 mAb, at 3 mg/kg or 1 mg/kg or placebo. We evaluated the safety and pharmacokinetics of reslizumab, and biologic activity was assessed by means of endoscopic evaluation of polyp size, symptoms, peripheral eosinophil counts, peripheral and local IL-5 levels, eotaxin levels, and eosinophil cationic protein levels. RESULTS: We demonstrated that a single injection of reslizumab up to 3 mg/kg is safe and well tolerated. Blood eosinophil numbers and concentrations of eosinophil cationic protein were reduced up to 8 weeks after treatment in serum and nasal secretions. Individual nasal polyp scores improved only in half of the treated patients for 4 weeks. Responders had increased IL-5 concentrations in nasal secretions at baseline compared with nonresponders, and logistic regression analysis revealed that increased nasal IL-5 levels (>40 pg/mL) predict the response to anti-IL-5 treatment. CONCLUSION: A single injection of anti-IL-5 reduces the size of nasal polyps for 4 weeks in half of the patients, and nasal IL-5 levels predict the response to anti-IL-5 treatment. CLINICAL IMPLICATIONS: Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.

Adolescent↗

Distinct features of chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Based on the presence of nasal polyps on endoscopy, chronic rhinosinusitis (CRS) may be clinically divided in CRS with nasal polyps and CRS without nasal polyps. It is unclear, whether CRS with nasal polyps and CRS without nasal polyps represent different disease entities or just different stages of one single disease. In case of one disease, only minor histopathological differences between CRS with small early-stage polyps (CRSNP((+))) and CRS without nasal polyps (CRSNP(-)) were expected. METHODS: Patients with CRSNP((+)) confined to the infundibular region or CRSNP(-) were selected. Histochemical and immunohistochemical characterization of ethmoidal mucosa was performed on formalin-fixed and paraffin-embedded tissue specimens. Frequency and distribution of eosinophils, neutrophils, mast cells, IgE(+) cells, macrophages, B- and T-cell subsets, natural killer cells, plasma cells and goblet cells were assessed. In addition, the thickness of the basal membrane was evaluated. RESULTS: Nine CRS patients without detectable polyps, and 11 patients with small early-stage polyps confined to the infundibular region were selected. Despite adjacent polyp stage, the amount of round cell infiltration (P < 0.05), number of eosinophils (P < 0.05), and plasma cells (P < 0.01) significantly differed in the ethmoidal specimens from patients of the two groups. CONCLUSION: Substantial histopathological differences were observed in ethmoidal mucosa of CRSNP((+)) and CRSNP(-) patients. Thus, the results of this investigation support the concept that CRS with nasal polyps and CRS without nasal polyps are two different disease entities rather than different stages of one single disease, but may also be interpreted as a higher degree of inflammation.

Adult↗

Degranulation of cystic fibrosis nasal polyp mast cells.

The ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non-CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non-CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non-CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non-CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non-CF specimens. Although eosinophils were observed in the non-CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non-CF nasal polyps with mast cell degranulation, a salient feature of CF specimens.

Adolescent↗

Expression of cell cycle regulatory proteins and analysis of apoptosis in normal nasal mucosa and in nasal polyps.

BACKGROUND: The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. METHODS: Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3'OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. RESULTS: We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti-Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. CONCLUSION: The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.

Adult↗

Keratinocyte growth factor and its receptor messenger RNA expression in nasal mucosa and nasal polyps.

To examine the potential biologic role of fibroblast growth factors (FGFs) in nasal polyps and nasal mucosa during chronic inflammatory conditions, we investigated messenger RNA (mRNA) expression of three members of the FGF family -- acidic FGF, basic FGF, and keratinocyte growth factor (KGF)-- in nasal polyp tissues, as well as in hyperplastic nasal mucosa. Using the sensitive method reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated that of the examined FGFs, KGF had the most abundant mRNA expression in nasal polyps and nasal mucosa. We also found that significantly higher levels of KGF mRNA were expressed in nasal polyps than in nasal mucosa, whereas mRNA expression of acidic FGF and basic FGF was relatively low in these tissues. In addition, we showed that KGF receptor mRNA was present in most of the nasal mucosa; however, none or little was expressed in nasal polyps. These results suggest that KGF might play an important role in nasal epithelial proliferation and that excessive synthesis of KGF in nasal polyp stroma may contribute to hypertrophy of the nasal mucosa in patients with chronic sinusitis associated with nasal polyposis.

Adult↗

Nasal polyps treated by beclomethasone nasal aerosol.

A double-blind cross-over study of the effect of insufflation of beclomethasone dipropionate 400 microgram per day for four weeks showed favourable results, as verified statistically, concerning nasal blockage at the end of the treatment period. Rhinomanometry also showed that the nasal patency was significantly improved during the beclomethasone period. There was also a tendency, though not statistically significant, for nasal secretion to react favourable. The polyps did not disappear during the active treatment period and short-term treatment with beclomethasone aerosol can thus only be used as an adjuvant to other models of therapy, whether medical or surgical, in nasal polyps. No clinical side-effects of any importance were observed during the study.

Administration, Intranasal↗

Update on nasal polyps: etiopathogenesis.

PURPOSE OF REVIEW: Nasal polyps is a common ENT disease with high medical failure and recurrence rate, reflecting unknown pathogenesis. The present review is an update on the etiopathogenesis of nasal polyps. RECENT FINDING: Several mechanisms have been proposed for the formation of nasal polyps, including allergy, mucosal allergy, autonomic imbalance, nitric oxide, superantigens, infection, abnormal transepithelial ion transport, mucopolysaccharide abnormality, mechanical obstruction and epithelial rupture. Eosinophils comprises more than 60% of the cell population. Activated T cells, mast cells and plasma cells are also increased compared with the normal nasal mucosa. The stroma has numerous mediators, including cytokines, growth factors, adhesion molecules, and immunoglobulins. Both Th1 and Th2 types of cytokines are upregulated independent of the atopic status. An increased production of GM-CSF, IL5, RANTES and eotaxin can contribute to chronic eosinophilic inflammation by regulating the migration, survival and activation of eosinophils. CONCLUSION: Nasal polyps is a multifactorial disease, with infectious, noninfectious, inflammation, anatomic and genetic abnormalities. Chronic inflammation remains the central major factor in nasal polyps.

Humans↗

Cysteinyl leukotriene 1 receptor expression in nasal polyps.

OBJECTIVES: The pathogenesis of nasal polyps, thought to involve complex interactions between different factors, is currently not fully understood. Recent studies have suggested the involvement of cysteinyl leukotrienes (CysLTs) in nasal polyp development. To further understand the role of CysLTs in polyp pathogenesis, we studied the expression of CysLT1 receptors in nasal polyps. METHODS: The study group comprised polyps removed endoscopically from 20 consecutive patients. Samples of ethmoid mucosa from 4 patients who underwent orbital decompression for Graves' ophthalmopathy were used as controls. The presence of CysLT1 receptors was determined with a rabbit anti-human anti-CysLT1 receptor polyclonal antibody. Cells with and without CysLT1 receptor expression were counted within the epithelial layer and stroma by means of light microscopy (40x magnification). RESULTS: There were significantly more cells expressing CysLT1 receptors in the stroma than in the epithelium in both nasal polyps and control specimens. The stroma of polyps also contained more CysLT1 receptor-expressing cells than did controls (29 x 10(3) +/- 7 x 10(3) versus 3 x 10(3) +/- 3 x 10(3) cells per square millimeter; p < .01). In the epithelium of polyps, there was significantly higher expression of CysLT1 receptors than in controls (7 x 10(3) + 3 x 10(3) versus 0 cells per square millimeter; p = .02). No significant differences in polyps were found between patients with and patients without Samter's triad and asthma. CONCLUSIONS: The significant up-regulation of CysLT1 receptors we found in both the stroma and the epithelium of nasal polyps suggests the presence of an inflammatory component in the pathogenesis of polyps, and possibly explains the efficacy of leukotriene modifiers in their treatment.

Biomarkers↗

Nasal polyps in cystic fibrosis: clinical endoscopic study with nasal lavage fluid analysis.

STUDY OBJECTIVES: Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group. PATIENTS AND STUDY DESIGN: The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype. RESULTS: The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found. CONCLUSIONS: There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.

Adolescent↗

Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyp epithelium.

BACKGROUND: The pathogenesis of nasal polyp disease is poorly understood. Recent evidence has suggested that nitric oxide (NO), an endogenous soluble gas vasodilator and inflammatory mediator, may be synthesised within the nasal cavity. Three nitric oxide synthase isoforms have been identified in humans, with the inducible isoform (iNOS) generally expressed in the setting of inflammation. OBJECTIVE: The aim of this study was to detect and localize iNOS expression in nasal polyp tissue, and compare these findings with normal nasal turbinate tissue. METHODS: We examined the expression and localisation of inducible nitric oxide synthase (iNOS) in human nasal airway specimens from patients undergoing elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA expression was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and localised by in situ hybridization. Densitometric data were analysed using Student's unpaired t-test. Adjacent sections were also examined for iNOS protein expression by immunohistochemistry. RESULTS: Semi-quantitative RT-PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was significantly increased in the five nasal polyps (P < 0.05). In situ hybridization studies revealed strong iNOS mRNA signal localized to the respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern was confirmed by immunohistochemistry. Localization to inflammatory cells or other subepithelial structures was not seen. CONCLUSIONS: We conclude that iNOS expression is upregulated in nasal polyp disease, and is localized to the polyp epithelial layer. These data reinforce the concept that the epithelial layer may be important in the pathogenesis of nasal disease, and suggest a potential role for NO in the formation of nasal polyps.

Epithelium↗

[Establishment of 2-dimensional gel electrophoresis map and analysis of proteomics from human nasal polyps].

OBJECTIVE: To establish 2-dimensional polyacrylamide gel electrophoresis (2-DE) map from human nasal polyps and normal nasal mucosa, and to identify differential expression proteins of 2-DE map. METHODS: Samples of nasal polyps and nasal mucosa (each sample group containing 7 cases) were obtained. The total proteins were extracted and separated by immobilized pH gradient (IPG)-based 2-DE. The silver-stained 2-DE was scanned with digital Imagescanner and analyzed with ImageMaster 2-DE Elite 4.01 software. To obtain peptide mass fingerprint (PMF) of differential protein spots, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used. The PMF was searched in Swiss-Prot and TreMBL database by Pept-Ident software, to identify differential expression proteins. RESULTS: The well-resolved, reproducible 2-DE maps of nasal polyps and nasal mucosa were established. For the polyps tissues, the average proteins spot of three 2-DE maps was 825+/-78; and 682+/-96 spot was matched with the average matching rate of 82.7%. The average deviations of matched spot position were (1.13+/-0.16) mm in IEF direction and (1.45+/-0.21) mm in SDS-PAGE direction, respectively. For the nasal mucosa tissues, the average proteins spot of three 2-DE maps was 936+/-62; and 821+/-78 spots were matched with the average matching rate of 87.7%. After comparing the 2-DE maps of nasal polyps and nasal mucosa tissues, the protein spots were 1,458 and 1,617 respectively; and 1,026 protein spots were matched. Forty differential expression protein spots were incised from silver staining gel randomly and digested in the gel by TPCK-Trypsin. Thirty-four PMFs were obtained by MALDI-TOF-MS and 24 differential proteins were identified. CONCLUSION: The well-resolved, reproducible 2-DE maps of human nasal polyps and nasal mucosa have been successfully established. Certain differential proteins related to the pathogenesis of human nasal polyps are identified.

Adult↗

[Effects of intranasal budesonide on the infiltration and activation of eosinophils in nasal polyps].

OBJECTIVE: To assess the effects of topical nasal steroid application on the infiltration and activation of eosinophils in nasal polyps. METHODS: Nasal polyps from intranasal budesonide treated patients (n = 16) and untreated patients (n = 16) were investigated. The samples were stained with histochemical and ABC immunohistochemical methods. RESULTS: The majority of eosinophils in nasal polyps were activated eosinophils. Compared with untreated polyps, the proportion of activated eosinophils (EG2+/eosinophil ratio) was significantly less in steroid-treated polyps. Although the numbers of total eosinophils and actived eosinophils were lower in steroid-treated polyps, both of the differences were not statistically significant. CONCLUSIONS: It emphasized that the actived eosinophils play a key role in the pathogenesis of nasal polyps. The effects of intranasal steroid treatment on the number of eosinophils (total and activated) was more profound then on the proportion of activated eosinophils.

Administration, Topical↗

Epithelial atypia and squamous metaplasia in nasal polyps.

Fifteen routine nasal polypectomy specimens submitted to our laboratory over an eight-month period were noted to show marked atypia within areas of squamous metaplasia to a degree suggestive of dysplasia. Reviewing the literature revealed little published work in this area, especially recently. Further nasal polyp cases from this, and a similar previous time period, were re-examined, and possible causes for these changes discussed.

Adult↗