Nasal wall compliance in vasomotor rhinitis.

Nasal compliance is a measure related to the blood volume in the nasal mucosa. The objective of this study was to better understand the vascular response in vasomotor rhinitis by measuring nasal cross-sectional area and nasal compliance before and after mucosal decongestion in 10 patients with vasomotor rhinitis compared with 10 healthy subjects. Nasal compliance was inferred by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of -10 cmH2O. Mucosal decongestion was obtained with one puff per nostril of 0.05% oxymetazoline. At atmospheric pressure, nasal cross-sectional areas were similar in the vasomotor rhinitis group and the healthy subject group. Mucosal decongestion did not induce any decrease of nasal compliance in patients with vasomotor rhinitis in contrast with healthy subjects. Our results support the hypothesis, already proposed, of an autonomic dysfunction based on a paradoxical response of the nasal mucosa in vasomotor rhinitis. Moreover, the clearly different behavior between healthy subjects and vasomotor rhinitis subjects suggests that nasal compliance measurement may therefore represent a potential line of research to develop a diagnostic tool for vasomotor rhinitis, which remains a diagnosis of exclusion.     

儿童过敏性结膜炎与变应性鼻炎的相关性及鼻眼联合防治效果分析

目的：探讨儿童过敏性结膜炎与变应性鼻炎的相关性研究及鼻眼联合防治的临床效果。方法：回顾性分析300 例儿童过敏性 结膜炎与310 例儿童变应性鼻炎患者的临床资料,对儿童过敏性结膜炎与变应性鼻炎的相关性进行分析后将所有患儿随机均分 为对照组与观察组,对照组采用常规点眼的方法进行治疗,观察组则采用鼻朗喷鼻联合人工泪液点眼进行治疗。比较两组临床疗 效及不良反应情况。结果：（1）300 例过敏性结膜炎患儿中,50 例（16.67%）并发变应性鼻炎;310 例变应性鼻炎患儿中,59 例 （19.03%）并发过敏性结膜炎（P＞0.05）;（2）109 例同时并发两种疾病患儿中,均进行眼结膜与鼻粘膜的刮片检查嗜酸性粒细胞, 其中60 例（55.05%）结膜刮片与67 例（61.47%）鼻粘膜刮片检测到嗜酸性粒细胞（P＞0.05）;（3）两组治疗前后BUT 及角膜荧光素 染色评分、症状评分、临床总有效率比较差异明显（P＜0.05）。结论：儿童过敏性结膜炎与变应性鼻炎具有一定的相关性;鼻朗喷鼻 联合人工泪液点眼治疗儿童合并变应性鼻炎的临床疗效显著。     

Expression and localization of the thromboxane A2 receptor in human nasal mucosa

Thromboxane A2 (TXA2) has been thought a potent mediator involved in allergic rhinitis, because TXA2 was recovered from the nasal lavage fluid of allergic rhinitis patients after allergen provocation and TXA2 receptor antagonists relief nasal allergic symptoms. In order to clarify the expression of TXA2 receptor in human nasal mucosa, we investigated TXA2 receptor mRNA expression and its protein localization by polymerase chain reaction (PCR) and immunohistochemistry, respectively. Human turbinates were obtained after turbinectomy from 10 patients with nasal obstruction refractory to medical therapy. RT-PCR analysis of total RNA from nasal mucosa demonstrated the expression of TXA2 receptor alpha mRNA. The immunohistochemical studies revealed that anti-TXA2 receptor alpha antibody labeled vascular smooth muscle cells, vascular endothelial cells, epithelial cells and submucosal glands in the nasal mucosa. The results may have an important clinical implication for understanding the role of TXA2 receptor on upper airway diseases such as allergic rhinitis and non-allergic rhinitis.     

Presence and location of endothelin and endothelin-binding sites in human nasal mucosa under normal and metaplastic conditions

The presence and site of production of endothelin-1 (ET-1) was investigated in biopsies obtained from the nasal mucosa of 10 healthy human subjects and 10 patients affected by chronic rhinitis. The presence and localization of receptors for ET-1 was also investigated. Bioptic fragments were examined by scanning electron microscopy. ET-1 was present in the vessels and in the respiratory epithelium of normal subjects, whereas in patients affected by epithelial metaplasia induced by chronic rhinitis, it was absent in the metaplastic epithelium and present in the endothelium and vascular wall. Receptors for ET (A- and B-receptor subtypes) were localized in the vessels of the nasal mucosa, both in normal and in pathological subjects. In particular, A-receptors were identified in the vascular wall, whereas B-receptors were mainly distributed in the endothelium. We suggest that ET-1 is involved in the homeostasis of nasal blood flow (shunting the blood toward the deep cavernous plexus and inducing mucosal swelling) by an autocrine and/or paracrine mechanism. Normal epithelium seems to be important in this mechanism, since it is able to produce ET. However, when pathologic conditions induce squamous or cuboidal metaplasia, the epithelium is no longer able to play this role.     

Comparative characterization of the microflora of the upper respiratory tract mucous membranes in bronchial asthma and allergic persistent rhinitis

A total of 250 patients with diagnosed bronchial asthma (BA) were examined by microbiological methods. Among them--188 children and 62 adults. In 87 patients the microflora of nasal mucosa was studied, in 40--of pharynx only and in 123 patients--both the nasal and the pharynx. For comparative analysis earlier data obtained in 69 patients with persistent allergic rhinitis (PAR) were used. The cultures isolated from the nasal mucosa of BA patients were shown to number 18 genera and 42 species, while among those isolated from pharynx mucosa 20 genera and 40 species. Monocultures were isolated from the nasal mucosa only in 23% of the examined patients and from the pharynx mucosa--only in 1.42%. Associations with different numbers of components were isolated from nasal and pharynx mucosa (2 to 6, 2 to 8 respectively). Staphylococcus aureus was regarded as the main species of nasal biocenosis in BA and PAR, as well as pharynx biocenosis in BA. Besides, in BA other Staphylococcus species (schleiferi, caprae, capitis, hominis, etc.), reversely related to the main species, could be isolated from both mucous membranes. Similarities and differences in microflora of biocenoses in both nosological forms, confirming links between PAR and BA, are considered.     

变应性鼻炎鼻黏膜组织重塑的研究及转化生长因子β1 在鼻黏膜中 的表达*

目的:探讨变应性鼻炎(allergic rhinitis AR)鼻黏膜组织是否存在重塑并检测与组织重塑密切相关的转化生长因子β1(TGF-β1)在AR患者鼻黏膜组织中的表达及意义。方法:取健康自愿者、轻度间歇性AR患者、重度持续性AR患者的中鼻甲黏膜组织各10例。苏木素伊红(HE)染色法观察嗜酸细胞浸润并测定上皮损伤情况;阿辛蓝-过碘酸-希夫(AB-PAS)染色法计数杯状细胞数;三色胶原(MT)染色测定细胞外基质沉积面积百分比。酶联免疫吸附试验(ELISA)测定组织中TGF-β1的表达。结果:①对照组无明显嗜酸细胞浸润,两鼻炎组较多嗜酸细胞浸润(P<0.01),②轻度AR组中仅上皮细胞损伤1级比对照组明显(P<0.01),重度AR组上皮损伤1、2、3级均比对照组明显(P<0.01),③两鼻炎组杯状细胞数明显多于对照组(P值均<0.01),④与对照组相比,轻度AR组胶原沉积面积增多,但无统计学意义(P>0.05),重度AR组明显增多(P<0.01),⑤TGF-β1在两鼻炎组黏膜中的表达均比对照组显著增高(P<0.01);重度AR组TGF-β1的表达均比轻度AR组增高,具有统计学意义(P<0.05)。结论:AR的鼻黏膜组织发生了重塑,表现为:上皮细胞损伤,杯状细胞化生,细胞外基质沉积,重度AR患者的鼻黏膜重塑更强,更广泛。TGF-β1积极参与了AR鼻黏膜组织的重塑过程。     

Experimental Sendai virus infection in laboratory rats. II. Pathology and immunohistochemistry

Intranasal inoculation of 5 to 8 week old specific pathogen-free Sprague-Dawley rats with 5 X 10(3) egg infectious doses of Sendai virus resulted in severe rhinitis, bronchiolitis and alveolitis. The most severe rhinitis occurred on postinoculation (PI) days 4-6, and pneumonia on day 4. Rhinitis and pneumonia persisted to PI day 21, with peribronchial lymphoid infiltration detectable at PI day 42. Immunohistochemical studies showed that Sendai virus antigens were present primarily in columnar epithelial cells of the respiratory mucosa of the nasal cavity and in bronchiolar and alveolar epithelium. Antigen was first detectable at PI day 1, was most prominent at days 3-4 and was undetectable after day 7. More antigen could be seen in the nasal mucosa than in the lung at any stage in the infection. These studies show that Sendai virus by itself is capable of evoking severe, although transient, rhinitis and pneumonia in laboratory rats free of other significant pathogens.     

Calpeptin通过抑制GATA3减轻变应性鼻炎大鼠炎症

摘要 目的：本研究旨在评估钙蛋白酶抑制剂calpeptin减轻变应性鼻炎大鼠炎症的作用并探讨其机制。方法：将20只雄性SD大鼠采用数字表法随机分为4组：正常组（Normal）、变应性鼻炎组（AR）、地塞米松干预AR组（DXMS+AR）、calpeptin干预AR组（Calpeptin+AR）。造模成功后,对大鼠AR症状进行行为学评分,对大鼠鼻黏膜组织切片以HE和PAS染色法观察鼻黏膜病理改变;对大鼠外周血以ELISA法检测总IgE、IL-4、IL-13水平;对大鼠鼻黏膜组织以免疫蛋白印迹法检测GATA3蛋白表达水平。单因素方差分析进行多组间比较,LSD- t检验进行组间两两比较。结果：与Normal组相比,AR组大鼠的鼻部过敏症状、鼻黏膜嗜酸粒细胞计数及外周血总IgE水平均升高,Calpeptin与地塞米松均能减轻气道炎症,减少嗜酸性粒细胞浸润,降低血清中OVA诱导的IgE的生成。探讨机制发现,酶联免疫吸附试验检测Th2细胞因子,与Normal组比较,AR组血清IL-4、IL-13水平均升高（P＜0.05）,而Calpeptin与地塞米松均能降低血清IL-4、IL-13水平（P＜0.05）。免疫蛋白印迹法检测大鼠鼻黏膜GATA3蛋白表达水平显示,与Normal组比较,AR组鼻黏膜 GATA3表达升高（P＜0.05）,而Calpeptin与地塞米松组鼻黏膜 GATA3表达均下降（P＜0.05）。结论：腹腔注射calpeptin能够减轻变应性鼻炎大鼠局部和全身过敏反应,其机制可能下调GATA3表达,影响Th2细胞的分化及细胞因子的分泌有关。     

变应性鼻炎模型小鼠鼻黏膜的形态学观察

目的:建立小鼠变应性鼻炎模型,观察小鼠鼻腔黏膜组织的重塑情况。方法:20只BALB/c小鼠被随机分为致敏组和对照组,使用卵清蛋白(OVA)诱导建立小鼠变应性鼻炎模型。通过HE染色观察小鼠鼻黏膜的大体重塑情况,吉姆萨染色观察嗜酸性粒细胞,阿辛蓝-过碘酸-希夫染色观察杯状细胞;酶联免疫吸附(ELISA)法检测小鼠血清中白细胞介素-4(IL-4)的水平。结果:小鼠变应性鼻炎模型的生物学行为评分为6.5±1.3,提示造模成功。与对照组相比,致敏组鼻腔黏膜出现上皮细胞脱落、坏死,杯状细胞增生,鳞状上皮化生,固有层和黏膜下层腺体增生、血管扩张,组织水肿,固有层内可见特征性的嗜酸性粒细胞浸润,造模后鼻腔黏膜结构存在重塑。致敏组小鼠鼻黏膜嗜酸性粒细胞计数及杯状细胞计数分别为(26.4±5.72)和(24.14±3.12),而对照组分别是(8.31±2.42)和(9.41±1.22),两组比较均具有统计学差异(P0.05);致敏组血清中白细胞介素4(IL-4)水平为(18.9±3.1)pg/ml,对照组为(8.3±1.4)pg/ml,致敏组显著高于对照组,差异有统计学意义(P0.05)。结论:通过卵清蛋白诱导建立的小鼠变应性鼻炎模型鼻腔黏膜存在组织重塑。     

Toll样受体2及Toll样受体4在大鼠实验性变应性鼻炎中的表达

目的研究Toll样受体2（Toll-like receptor2,TLR2）及Toll样受体4（TLR4）在实验性变应性鼻炎大鼠鼻黏膜中的表达及脂多糖（Lipopolysaccharide,LPS）对其表达的影响。方法SD大鼠48只随机分为正常对照组（A组）;变应性鼻炎组（B组）：经腹腔注射及鼻腔滴入卵清白蛋白（Ovalbumin,OVA）建立变应性鼻炎（Allergic rhinitis,AR）模型;变应性鼻炎＋LPS刺激组（C组）：大鼠激发成变应性鼻炎模型后再以LPS滴鼻。用逆转录聚合酶链反应（RT-PCR）方法检测鼻黏膜中TLR2 mRNA、TLR4 mRNA的表达。结果B、C组大鼠均成功激发为AR动物模型;各组鼻黏膜中均有TLR2 mRNA、TLR4 mRNA表达;各组间TLR2 mRNA的表达差异无统计学意义（P〉0．05）。B、C组TLR4 mRNA的表达较A组高（P〈0．01）;C组TLR4 mRNA表达较B组增高（P〈0．01）。结论AR大鼠有TLLR4的表达增高;LPS刺激后TLR4表达进一步增高,说明TLR4可能参与AR的发病。TLR2在AR大鼠中的表达未见增高;LPS刺激后。TLR2表达未见进一步增高,TLR2与变应性鼻炎的关系有待进一步研究。     

Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal polyposis

Background

Peroxisome proliferator-activated receptor (PPAR) α, βδ and γ are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested.

Methods

Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone). Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification.

Results

mRNA expression of PPARα, PPARβδ, PPARγ was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARα and PPARγ than normal nasal mucosa and these levels were, for PPARγ, further reduced following steroid treatment. PPARγ immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPARγ immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment.

Conclusion

The down-regulation of PPARγ, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPARγ might be of importance in long standing inflammations.     

May nasal hyperreactivity be a sequela of recurrent common cold?

Respiratory viral infections may worsen bronchial hyperreactivity. However, there is no data on the possible role of recurrent infectious rhinitis in nose hyperreactivity. This study was therefore designed to investigate whether subjects suffering from recurrent common cold have nasal hyperreactivity, assessed by histamine nasal challenge. This study included a group of 40 patients (19 males, mean age 34.1 years) with history of at least five episodes of common cold in the previous year, but without documented allergy, and twenty healthy subjects (8 males, mean age 32.3 years) were enrolled as control group, all of whom were non-allergic. Nasal provocation test with histamine was performed in all subjects. Nasal provocation test with histamine induced a 200% increase in nasal resistance after provocation in 24 (60%) patients suffering from recurrent viral rhinitis. No normal subject had an increase >180% in nasal resistance. There was a significant difference between the patient group and the control group (p<0.05). In conclusion, this study shows that nasal hyperreactivity might be a sequela of recurrent common cold. Further studies should be conducted to confirm this preliminary finding.     

甲苯-2,4-二异氰酸酯经鼻致敏建立羊变应性鼻炎模型

目的旨在建立鼻腔宽敞的大型动物变应性鼻炎模型,初步探讨其实用性。方法①南江黄羊4只行鼻部解剖,记录鼻腔解剖学参数。②南江黄羊12只,8只为模型组,15%甲苯-2,4-二异氰酸酯（TDI）橄榄油溶液滴鼻致敏,4只为对照组,使用橄榄油液。记录建模过程中黄羊症状体征评分,建模完成后测定黄羊鼻腔灌洗液组胺含量并行鼻黏膜组织病理学检查。③将建模成功的黄羊随机分为A组（布地奈德治疗组）和B组（生理盐水对照组）,记录治疗前后症状体征评分变化,评价该模型对药物治疗的反应。结果①黄羊鼻腔宽敞,鼻腔解剖结构与人类极其相似。②TDI致敏后,与对照组相比,模型组8只黄羊均出现典型变应性鼻炎症状体征,鼻腔灌洗液中组胺含量明显增高,差异均有统计学意义（P〈0.01）;组织病理学检查见黄羊鼻黏膜下组织水肿,血管扩张,固有层内散在或灶性以嗜酸性粒细胞为主的炎症细胞浸润。③布地奈德治疗组症状体征评分下降,与对照组相比差异有统计学意义（P〈0.05）。结论成功建立大型动物变应性鼻炎模型,不但可用于研究药物疗效,还可用于判定新的物理和手术治疗安全性及有效性。     

Expression of Toll-like Receptor 9 in nose, peripheral blood and bone marrow during symptomatic allergic rhinitis

Background

Allergic rhinitis is an inflammatory disease of the upper airway mucosa that also affects leukocytes in bone marrow and peripheral blood. Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides found in bacterial and viral DNA. The present study was designed to examine the expression of TLR9 in the nasal mucosa and in leukocytes derived from different cellular compartments during symptomatic allergic rhinitis.

Methods

The study was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects, serving as controls. Nasal biopsies were obtained before and after allergen challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled outside and during pollen season. The expression of TLR9 in tissues and cells was analyzed using immunohistochemistry and flow cytometry, respectively.

Results

TLR9 was found in several cell types in the nasal mucosa and in different leukocyte subpopulations derived from bone marrow, peripheral blood and nasal lavage fluid. The leukocyte expression was generally higher in bone marrow than in peripheral blood, and not affected by symptomatic allergic rhinitis.

Conclusion

The widespread expression of TLR9 in the nasal mucosa along with its rich representation in leukocytes in different compartments, demonstrate the possibility for cells involved in allergic airway inflammation to directly interact with bacterial and viral DNA.     

In vivo intranasal anti-CD23 treatment inhibits allergic responses in a murine model of allergic rhinitis

Although CD23-dependent transcytosis of IgE and IgE-derived immune complexes across respiratory epithelial cells is likely to play a pivotal role in the initiation and development of airway allergic inflammation, there is currently a lack of physiological support for this phenomena to suggest that the targeting of CD23 could be used as a means of therapeutic intervention. The present study was designed to detect the CD23 expression in the nasal mucosa of allergic rhinitis (AR) murine model by immunohistochemistry and western blotting, and to investigate whether intranasal anti-CD23 treatment could inhibit allergen-induced upper airway inflammation in the AR model. This is the first report to show that CD23 was constitutively expressed in murine nasal epithelial cells, and its expression was significantly up-regulated in the AR murine model. In vivo, the up-regulation of CD23 expression was correlated with increased serum IL-4 levels. Following intranasal anti-CD23 treatment, nasal symptoms were alleviated and histopathologic examination showed a significant decrease in eosinophilic infiltration. Meanwhile, ELISA analysis showed levels of serum leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin (OVA)-specific IgE and IL-4 also significantly decreased, as were LTC4 and OVA-specific IgE in the nasal lavage fluid. Furthermore, Western blotting analysis showed that ECP expression in the nasal mucosa was down-regulated. Finally, flow cytometric analysis revealed anti-CD23 treatment inhibited Th2 cell responses. These results indicate that intranasal anti-CD23 treatment can reduce allergic responses in a murine model of allergic rhinitis.     

Construction and delivery of gene therapy vector containing soluble TNFalpha receptor-IgGFc fusion gene for the treatment of allergic rhinitis

Tumor necrosis factor alpha plays primary role in the pathogenesis of inflammatory diseases. TNFalpha is essential for antigen-specific IgE production and for the induction of Th2-type cytokines. The lack of TNFalpha inhibited the development of allergic rhinitis. In this study, the chimeric gene of soluble TNF receptor and IgGFc fragment (sTNFR-IgGFc) was cloned into the EBV-based plasmid pGEG. When the plasmid pGEG.sTNFR-IgGFc was transferred to endothelium cell, a considerable expression of the sTNFR-IgGFc fusion protein was detected. Moreover, the expression product in the supernatant could antagonize the cytolytic activity of TNFalpha on L929 cells. Then the plasmid was delivered into nasal mucosa of allergic rhinitis mice to determine its effect on this animal model. Results showed that symptoms in treated group were improved. Pathological examination showed the numbers of eosinophil, mast cell and IL-5(+) cells in treated groups were reduced compared with placebo group. These data showed that pGEG.sTNFR-IgGFc expression plasmid is potential for the treatment of allergic rhinitis, and suggest that the antagonist of TNFalpha may provide a new approach for the treatment of allergic rhinitis.