Morphological changes of nasal and duodenal mucosa in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is an inherited multisystemic disorder that results in generalized dysfunction of exocrine glands. In patients with cystic fibrosis dyscrinia with affection of exocrine glands function is a main problem of the upper and lower respiratory tract. In addition to chronic obstructive pulmonary disease, chronic sinusitis, nasal polyposis and hypertrophy of inferior turbinates with nasal airway obstruction are typical signs. To understand pathophysiological mechanisms in CF and to correlate morphological findings with clinical symptoms, investigations of nasal mucosa are important. METHODS: Tissue samples of inferior turbinates were taken during nasal surgery from 7 children, ranging from 3 to 11 years of age between September 1998 and May 2000. Histological sections were cut followed by a light- and electron microscopical examination (EM 902 A Zeiss). Additionally, specimens of duodenal mucosa were investigated. RESULTS: In comparison with sections of normal nasal mucosa the lamina propria mucosae shows different morphological changes. Under a thick layer of respiratory epithelium with a high portion of goblet cells and particulary vacuoles there is an edematous subepithelial area. The capillary layer is reduced and the seromucous glands show an atypical morphological structure with widely mucous cells and cystic dilatation. On an ultrastructural level the glandular cells show atypical and inhomogeneous glandular droplets in the supranuclear cell portion. A viscous secretion was detectable at the glandular lumen. The nucleus contains dispersed chromatin as a sign of increased activity and the structures of Golgi apparatus were obviously detectable. CONCLUSIONS: In respective literature studies on the different morphological changes on light- and electron microscopical level in CF-associated rhinopathies are rare. This histological study demonstrated various morphological changes of nasal mucosa and shows a correlation between the glandular dysfunction and the typical symptoms in CF. Additionally a comparison with ultrastructural findings of CF-enteropathies is proposed. These findings could help to look at new aspects in the pathophysiology for patients with CF.     

Tenascin在鼻息肉组织中的表达及其临床意义

目的：探讨Tenascin(TN)在鼻息肉组织中的表达和分布特征及其在鼻息肉发生中的可能作用。方法：采用免疫组化链霉菌抗生物素蛋白—过氧化物酶(SP)法检测24例鼻息肉标本(鼻息肉组)和15例慢性肥厚性鼻炎下鼻甲标本(下鼻甲组)中TN的表达，并以5例健康者(对照组)下鼻甲黏膜作对照。结果：鼻息肉组和下鼻甲组黏膜上皮细胞及腺上皮细胞均表达TN；鼻息肉组TN的黏膜上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；鼻息肉组TN的腺上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；对照组下鼻甲组织中黏膜上皮及腺体几乎检测不到TN的表达；鼻息肉组腺体TN阳性率明显高于下鼻甲组(P＜0．05)。结论：TN在鼻息肉组织中的高表达与鼻息肉的发生、发展相关；TN在鼻腔内的表达细胞是黏膜上皮细胞和浆液性腺上皮细胞。     

Nasal polyps: a comparative study of morphologic and etiopathogenetic aspects

16 nasal polyps belonging to 10 male subjects aged between 40 and 70, have been removed during the same number of ethmoidectomies; the polyps have been sectioned and specimens of mucosa corresponding to the pedicle and to the different parts of the body have been collected. During the operation parts of the mucosa of the inferior turbinates were removed. All the specimens have been prepared and observed at the scanning electron microscope. The epithelium of the inferior turbinates, of the small polyps and of the apical part of all polyps were almost normal. Marked alterations of the epithelial layer have been observed in bigger polyps. Surface characteristics of nasal polyps seem to be influenced by their relationship with neighbouring structures and by their position in the nasal cavity, but mostly by their size. On the basis of these findings the authors discuss the most recent etiopathogenetic theories of nasal polyps. They finally describe some peculiar findings concerning the mucosal layer of the polyps and of the inferior turbinates of three confirmed allergic subjects and discuss their possible clinical implications.     

Inflammatory cells in nasal mucosa and nasal polyps

OBJECTIVE: Since some controversy exists concerning the frequency of inflammatory cells in nasal polyps, we have compared the frequency of tissue inflammatory cells (lymphocytes, neutrophils, eosinophils and plasma cells) including 11 kinds of lymphocyte subsets in the same specimens of nasal mucosa and nasal polyps. METHODS: Histopathological observations and flow cytometric analyses were performed on eight mucosal specimens of the inferior turbinates of patients with nasal polyps and on 13 polyp specimens. RESULTS: Nasal polyps contained significantly more eosinophils, neutrophils and plasma cells than nasal mucosa, and EG2+ cells (activated eosinophils) were significantly more frequent in nasal polyps than in nasal mucosa. Flow cytometric analysis showed that there were no significant differences in the frequencies of lymphocytes and lymphocyte subsets (CD1+, CD2+, CD3+, CD5+, CD7+, CD4+, CD8+, CD10+, CD19+, CD20+ and HLA-DR+ cells) including CD4/8 ratios between nasal mucosa and polyps, though, both nasal mucosa and polyps contained significantly more lymphocytes than eosinophils, neutrophils or plasma cells. The T cell lineage (CD2+, CD3+, CD5+ and CD7+ cells) was found in high frequency and B cell lineage (CD10+, CD19+ and CD20+ cells) in low frequency in both nasal mucosa and polyps. The frequency of HLA-DR+ cells (most of which were activated T cells) was not significantly different between nasal mucosa and nasal polyps. CONCLUSION: Histopathological and flow cytometric analyses were performed on the composition of inflammatory cells in nasal mucosa of the inferior turbinates and in polyps from the same patients. The elevated numbers of activated eosinophils, neutrophils and plasma cells in nasal polyps compared with nasal mucosa suggest that inflammatory processes play important roles in the pathophysiology of nasal polyps. The frequencies of lymphocytes and lymphocyte subsets were not significantly different between these two tissues.     

Histopathological verification of clinical indications to partial inferior turbinectomy.

Surgical treatment in cases where disturbances of the nasal patency causes changes in the nasal inferior turbinates is controversial. The authors performed light- and electron microscopy and morphometric examinations of the mucous membrane of the nasal inferior turbinates obtained after partial inferior turbinectomy in patients with vasomotor and perennial allergic rhinitis and compensation hypertrophy of the nasal inferior turbinate accompanied by nasal deviation of the septum. In specimens obtained from patients with vasomotor rhinitis, a small number of glands and fibrosis of the lamina propria was observed. In specimens obtained from perennial allergic rhinitis patients, plenty of glands and large oedema was observed. In the group with compensatory hypertrophy of the inferior turbinate, normal glands and fibred areas around the vessels were observed. The largest histopathological changes of degeneration and hypertrophy of the nasal mucosa were observed in vasomotor rhinitis patients. Histopathological examination of nasal mucosa slides confirmed the usefulness of a partial inferior turbinectomy, but only in vasomotor rhinitis patients.     

神经生长因子及其受体在鼻息肉中的表达及意义

目的 探讨神经生长因子(nerve growth factor,NGF)及其受体在鼻息肉组织中的表达。方法 采用免疫组化ABC法,检测20例鼻息肉组织(鼻息肉组)及6例正常下鼻甲黏膜(对照组)中NGF及其受体的表达。结果 对照组：正常下鼻甲黏膜中NGF及其受体的表达呈阴性;鼻息肉组：其黏膜上皮层和黏膜下层中NGF染色阳性率分别是90%(18/20)和95%(19/20);在鼻息肉组织同样位置发现了NGF的高亲和性受体TrKA(Tyrosine kinase A)高表达,在纤毛上皮细胞和腺上皮细胞中发现了NGF的低亲和性受体P75高表达。结论 NGF在鼻息肉组织中具有高表达特征,表明NGF在鼻息肉发生发展机制中发挥着重要作用。     

Fas及Bcl-2在鼻息肉组织中的表达及意义

目的：探讨Fas和Bcl 2在鼻息肉组织中的表达及与鼻息肉发病的关系。方法：应用S P免疫组化法检测36例鼻息肉组织及19例下鼻甲组织中Fas和Bcl 2的表达情况。结果： （1）Fas在鼻息肉上皮及腺上皮的表达弱于对照组（P＜0.05）；（2）Bcl 2在鼻息肉上皮及腺上皮的表达强于对照组（P＜0.05）；（3）鼻息肉上皮细胞中Fas、Bcl 2蛋白的表达无相关性（P＞0.05）。结论：（1）Fas和 Bcl 2在鼻息肉发生发展中起重要作用；（2）在NP上皮细胞中， Fas和Bcl 2无相关性，因此这两种凋亡基因在NP的形成过程中各起独立作用，协调抑制NP上皮细胞的凋亡。     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

鼻黏膜中Toll样受体5的表达

目的研究鼻黏膜中Toll样受体5(Toll-likereceptor-5,TLR-5)的表达以了解TLR-5在鼻黏膜天然免疫中的作用。方法鼻息肉和下鼻甲组织从接受鼻内镜手术治疗的慢性鼻及鼻窦炎和鼻中隔偏曲患者取得。应用免疫组化法检测17例鼻息肉和13例下鼻甲黏膜中TLR-5蛋白的表达,应用实时荧光定量RT-PCR(real-time fluorescentquantitative RT-PCR,real-time FQ-RT-PCR)检测14例鼻息肉和9例下鼻甲黏膜中TLR-5 mRNA的表达。结果在所有标本中均检测到TLR-5 mRNA和蛋白表达。免疫组化显示TLR-5蛋白主要表达于鼻黏膜上皮细胞和腺体上皮细胞。在细胞核和细胞浆中均有表达。在鼻黏膜上皮,染色最强的区域位于黏膜上皮表面一侧的细胞膜和细胞核。另外在间质单核样炎症细胞及NK细胞也有表达。鼻息肉组织中TLR-5蛋白表达指数5.529±0.653较下鼻甲2.346±0.619增高,差异有统计学意义(Z=-3.107,P=0.002)。结论本次研究确认了TLR-5在鼻黏膜和鼻息肉组织的表达,鼻息肉组织中TLR-5表达的增高可能与鼻息肉内持续的炎症状态有关。提示TLR-5有可能成为鼻息肉、慢性鼻及鼻窦炎一个新的治疗靶点。     

Expression patterns of galectin-1 and galectin-3 in nasal polyps and middle and inferior turbinates in relation to growth regulation and immunosuppression

BACKGROUND: The term nasal polyposis describes benign growth processes in the nasal and sinus mucosa, which are mainly located in the middle meatus and never in the inferior meatus. As a step to define the biochemical determinants relevant for growth regulation, we focused on endogenous lectins known for anti-apoptotic (galectin-3) and immunomodulatory (galectin-1) activities. DESIGN: Using computer-assisted microscopy, we performed an immunohistochemical investigation defining the quantitative parameters of expression of galectin-1 and galectin-3 in 10 nasal polyps, 10 middle turbinates, and 10 inferior turbinates, all of which were obtained from surgical resection. RESULTS: Our data show that galectin-3 expression is markedly (P<.001) higher in nasal polyps than in turbinates. No relation to the allergic status was discovered. Galectin-1 expression is higher in nasal polyps than in middle turbinates (P<.001) in nonallergic patients compared with allergic ones (in glandular epithelium, P =.009; in connective tissue, P =.006). The lowest galectin-1 expression was observed in the middle turbinate. CONCLUSIONS: These data are in line with a positive influence of galectin-3 on growth and an immunoregulatory role of galectin-1, mimicking an increased expression dependent on glucocorticoid.     

Clinical aspects and distribution of immunologically active cells in the nasal mucosa of patients with nasal polyps after endoscopic sinus surgery and treatment with topical corticosteroids

Summary Clinical parameters of 72 patients who were operated upon for nasal polyps were evaluated as well as biopsy specimens of the mucosa of the middle and inferior turbinates of 41 of these patients. Biopsies were taken at the time of endoscopic sinus surgery (ESS), after 6 months and after 1 year in 23 patients. During the follow-up period the patients were treated with topical corticosteroids (budesonide). At the time of ESS significantly more CD8+ (suppressor/cytotoxic) cells than CD4+ (helper/inducer) cells were found in the middle and inferior turbinates. At 6 months significantly more CD4+ cells were found than at the time of ESS, whereas at 1 year the number of CD4+ cells had decreased and was lower than at 6 months. These data support the theory that the occurrence of nasal polyps is associated with T-cell-dependent disturbances. Clinical evaluation revealed that most of the patients with chronic airway obstruction had better pulmonary functions postoperatively or required less medication for lung disease. These findings show that ESS combined with topical corticosteroids has a positive effect on upper and lower respiratory tract pathology. Correspondence to: A. E. Stoop     

MUC5AC在人类鼻息肉及下鼻甲黏膜上皮的表达

目的 :探讨MUC5AC与鼻息肉及慢性肥厚性鼻炎黏液过量分泌的关系。方法 :免疫组织化学ABC法检测 2 7例鼻息肉、19例慢性肥厚性鼻炎下鼻甲及 9例正常下鼻甲黏膜上皮MUC5AC的表达。结果 :鼻息肉黏膜上皮及慢性肥厚性鼻炎下鼻甲黏膜上皮MUC5AC阳性细胞表达率明显高于正常下鼻甲黏膜上皮 (P <0 .0 5 ) ,且MUC5AC阳性表达细胞主要为杯状细胞。结论 :MUC5AC在鼻息肉及慢性肥厚性鼻炎下鼻甲黏膜上皮呈高表达 ,且阳性细胞为杯状细胞 ,表明MUC5AC确实对鼻息肉及慢性肥厚性鼻炎的黏液过量分泌起了一定作用。     

血管通透性因子在鼻息肉中的表达及意义

目的探讨血管通透性因子（ｖａｓｃｕｌａｒｐｅｒｍｅａｂｉｌｉｔｙｆａｃｔｏｒ，ＶＰＦ）在鼻息肉组织中的表达及意义。方法将９例鼻息肉标本及８例下鼻甲粘膜标本行ＶＰＦ及其受体ｆｌｋ１的免疫组化染色，光镜观查。结果ＶＰＦ在鼻息肉组织的血管内皮细胞和腺体细胞的表达明显高于下鼻甲组织（Ｐ＜０．０１，Ｐ＜０．０５），ｆｌｋ１在血管内皮细胞的表达明显高于下鼻甲组织（Ｐ＜０．０１）。结论ＶＰＦ对鼻息肉发生过程中组织极度水肿的产生可能有非常重要的作用。     

Long-term results of inferior turbinate reduction with argon plasma coagulation

OBJECTIVES: Surgical reduction of the inferior turbinates is a commonly used therapy in patients with hyperplastic inferior turbinates when medical management remains ineffective. Current surgical methods have disadvantages (e.g., necessity of nasal packing, extended postoperative swelling, and high costs). Theoretical considerations render argon plasma coagulation (APC) a promising new therapeutic approach. STUDY DESIGN: In a prospective study, 121 patients with chronic nasal obstruction were treated for inferior turbinate reduction with APC. Hyperplasia of the nasal turbinates was diagnosed rhinoscopically and endoscopically and confirmed rhinomanometrically. The mean follow-up period was 12 months, ranging from 10 to 16 months. The treatment results were evaluated by a questionnaire, rhinomanometric findings, and electron microscopic studies of the nasal mucosa. In 50 patients a ciliary function test was performed preoperatively and postoperatively. METHODS: Argon plasma coagulation, a high-frequency electrosurgery, has been used for volume reduction of the inferior turbinate in local anesthesia. RESULTS: Seventy-six percent of the patients reported an improvement of the postoperative swelling within the first week. After 6 weeks, macroscopically the turbinates were re-epithelialized by normal mucosa in 63% of the patients. Electron microscopic studies after 3 months verified normal cilia. After 12 months, 83% of the patients stated that they had a better nasal airflow than preoperatively. Crust formation was minimal. No bleeding or impaired ciliary function occurred. Ninety-five percent of the patients were willing to undergo the same operation again. CONCLUSION: The long-term results have proved APC to be an effective and easy-to-perform alternative for inferior turbinate reduction with comparable results to other established surgical methods.     

血管通透性因子在鼻息肉中的表达及意义

目的 探讨血管通透性因子（ｖａｓｃｕｌａｒ ｐｅｒｍｅａｂｉｌｉｔｙ ｆａｃｔｏｒ，ＶＰＦ）在鼻息肉组织中的表达及意义。方法 将９例鼻息肉标本及８例下鼻甲粘膜标本行ＶＰＦ及其受体ｆｌｋ－１的免疫组化染色，光镜观查。结果 ＶＰＦ在鼻息肉组织的血管内皮细胞和腺体细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１，Ｐ〈０．０５），ｆｌｋ－１在血管内皮细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１）。结论 ＶＰＦ对鼻     

A histological study of formation and growth of nasal polyps

Chronic infection and allergy are considered to be the two major etiologic factors of nasal polyps. Whatever its cause may be, the initial phase of nasal polyp formation is represented by increased exudation from vessels, edema of the lamina propria and the bulging of the nasal mucosa. Nasal polyps were histologically classified into three types: edematous type, glandular and cystic type (ductal type) and fibrous type. Those of the edematous type and the glandular and cystic type are in the active stage of tissue reaction because of permeation of vascular fluid and marked infiltration of round cells. Contrastingly, the fibrous type polyps are in the healing stage of tissue reaction because of marked proliferation of fibroblasts and collagen fibers. The morphological structure of the nasal glands involved in the bulging mucosa determines the type of nasal polyps, whether edematous type or glandular and cystic type.     

Ultrastrukturelle Veränderungen der Nasenschleimhaut des Menschen nach Abusus von topischen α-Sympathomimetika

BACKGROUND: Long-term abuse of decongestive nasal drops causes rhinitis medicamentosa due to cytotoxic and ciliary-toxic effects. Nasal obstruction is caused by rebound swelling when the decongestive effect has disappeared. The patient starts using nasal drops more frequently as a result of tachyphylaxis. PATIENTS AND METHODS: Tissue samples from human inferior turbinates from 22 patients who had overused decongestive nose drops were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. The findings were photo-documented using a light- and transmission electron microscope. Biopsies from ten patients without chronic inflammation of the nasal mucosa were used as controls. RESULTS: The electron microscopic investigations revealed epithelium showing severe damage corresponding to regions with hyperplastic and metaplastic changes. Loss of ciliated cells was observed. Under a thick basal membrane, ultrastructural changes to the endothelial lining, such as openings and rupture of the basal lamina, were detected. Prominent endothelial cells were conspicuous. CONCLUSIONS: Rhinitis medicamentosa is a drug-induced injury to human nasal mucosa associated with the prolonged abuse of topical nasal decongestants. Loss and destruction of ciliated epithelial cells are the morphological correlation to the disturbance of mucociliary clearance. Endothelial cells of capillaries, in particular, revealed ultrastructural changes indicative of increased permeability with consecutive interstitial edema.