抗原长期刺激致变应性鼻炎豚鼠模型鼻黏膜重塑的研究

目的:观察抗原长期刺激致变应性鼻炎豚鼠模型鼻黏膜重塑的特点。方法:Hartley豚鼠48只,随机分为6组(每组8只),即实验组用卵清蛋白(OVA)激发(OVA2W组、OVA6W组和OVA12W组),对照组用生理盐水激发(Sal2W组、Sal6W组和Sal12W组)。OVA制备变应性鼻炎动物模型,抗原刺激分别持续2W、6W和12W,在最后一次激发24h后行鼻腔灌洗、取鼻黏膜组织。ELISA法检测鼻腔灌洗液中OVA特异性免疫球蛋白(OVA-sIgE)、嗜酸粒细胞阳离子蛋白(ECP)含量;鼻黏膜组织切片采用苏木精-伊红、AB-PAS和MT法染色,计数鼻黏膜上皮杯状细胞数量,测量上皮细胞损伤程度、基膜胶原含量;免疫组织化学法检测鼻黏膜组织转移生长因子β1(TGF-β1)的表达。结果:①OVA6W、OVA12W组与OVA2W组比较,OVA-sIgE含量均差异有统计学意义(均P<0.05),而ECP含量在3个实验组中无明显差别;实验组与相应的对照组比较,OVA-sIgE、ECP含量均差异有统计学意义(均P<0.01)。②OVA6W、OVA12W组与OVA2W组比较,0级、1级上皮细胞损伤均差异有统计学意义(均P<0.01);实验组0级、1级上皮损伤与相应的对照组相比差异有统计学意义(均P<0.05)。③鼻黏膜杯状细胞增生和基膜胶原沉积,OVA6W、OVA12W组与OVA2W组比较均差异有统计学意义(均P<0.01);对照组杯状细胞数均较相应的实验组明显减少(均P<0.05);Sal6W、Sal12W组基膜胶原沉积均较相应的实验组明显减少(均P<0.05)。④OVA6W、OVA12W组与OVA2W组比较,TGF-β1的表达均差异有统计学意义(均P<0.01);实验组与相应的对照组比较,TGF-β1的表达均差异有统计学意义(均P<0.01)。结论:鼻黏膜上皮细胞损伤、杯状细胞增生和细胞外基质胶原沉积是变应性鼻炎鼻黏膜组织重塑的特点;在抗原激发早期,表现为上皮损伤,与重塑相关的细胞因子表达增强,随着抗原刺激延长,表现出腺体增生和胶原沉积的特征越明显。     

Histamine and the nasal vasculature: the influence of H1 and H2-histamine receptor antagonism

The aim was to determine the effect of H₁-and H₂-receptor blockade on histamine-induced changes in nasal airways resistance and levage protein concentrations. Normal subjects were pretreated with oral cetirizine or ranitidine in a double-blind and randomized manner. Measurements of the concentration of total protein and albumin in nasal a lavage fluid together with nasal airway resistance were made before and after challenge. any effect of treatment was assessed by comparing the areas under the time-response curves. In all nine subjects available for analysis histamine caused an immediate increase in all measurements. Ranitidine reduced the maximum increase in nasal airway resistance, but this effect was significant only in combination with cetirizine. The increase in lavage total protein and albumin concentrations was almos completly abolished by cetirizine, whereas ranitidine had less effect. We conclude that the histamine H₁-receptor has the greatest effect on changes in nasal vascular permeability induced by topical histamine, whereas the H₂-receptor has the greatest effect on nasal obstruction.     

The effect of topical sodium cromoglycate on intranasal histamine challenge in allergic rhinitis

Topical sodium cromoglycate is used to treat allergic diseases of the upper and lower airways. To investigate its mechanisms of action, intranasal histamine challenge was used in nine subjects with perennial allergic rhinitis. After a preliminary day where subjects’reactivity thresholds (D100) for histamine were determined, intranasal sodium cromoglycate was administered in a double-blind, placebo-controlled fashion. Graded (D100/3, D100, D100X3), sequential challenges were performed on days 1 and 21 of each course, and responses measured by changes in nasal airway resistance, sneezes, secretion volume and secretion content: total protein, lysozyme and mucin. After a single dose of sodium cromoglycate, there was no change in resistance, but secretion volumes fell significantly (3.12 ml/5 min c. i.2.83-3.4; placebo 3.61,c. i.3.32–3.90: P= 0.026). After a 3-week-course, there was a significant fall in resistance (4.29 cm H₂O/l/s, c. i.3.85–4.72; placebo 5.45,c. i.5.01–5.88: P < 0.0001). No change in other parameters was observed. Thus, in perennial allergic rhinitis, intranasal sodium cromoglycate has both short- and long-term effects on nasal reactivity to histamine challenge. Acutely, there is a reduction in nasal lavage fluid volume which may be the result of reduced irritant receptor activity. After a 3-week course, there is a reduction in nasal resistance responses, a possible anti-inflammatory effect.     

炎性细胞在变应性鼻炎患者鼻黏膜中的观察

目的 探讨变应性鼻炎患者鼻黏膜组织中炎性细胞的变化及与变应性鼻炎的关系。方法 选择55例发作期变应性鼻炎患者及123例健康者，采用刮匙在下鼻甲黏膜处刮拭涂片，用Wright染色，进行细胞学检测，并进行统行学分析。结果变应性鼻炎发作期患者黏膜细胞发生了显著变化，中性粒细胞及嗜酸粒细胞的数量显著增加（P〈0．001），淋巴细胞明显增加（P〈0.05），而脱落上皮细胞显著减少（P〈0．001）。结论 炎性细胞是变应性鼻炎发病机制中诸多因素之一，深入了解这一作用对于指导临床治疗有重要的意义。     

胸腺基质淋巴细胞生成素在变应性鼻炎模型小鼠鼻黏膜中的表达

目的：探讨胸腺基质淋巴细胞生成素（TSLP）在变应性鼻炎模型小鼠鼻黏膜中的表达。方法：将20只6～8周BALB／c小鼠随机分为变应性鼻炎组和自然对照组,每组10只。以鸡卵清蛋白致敏建立变应性鼻炎模型。组织标本石蜡包埋,采用免疫组织化学方法和荧光PCR方法检测TSLP在小鼠鼻黏膜中的表达。结果：自然对照组鼻黏膜未见明显TSLP表达,变应性鼻炎组鼻黏膜可见明显TSLP表达。结论：TSLP在变应性鼻炎的鼻黏膜中表达。     

鼻内类固醇激素对变应性鼻炎动物模型鼻腔黏膜的影响

目的:通过变应性鼻炎(AR)动物模型观察鼻内类固醇激素对鼻腔黏膜的影响。方法:36只SD大鼠随机分为3组:鼻内类固醇激素组(A组),AR模型组(B组)和正常对照组(C组)。A、B组以卵清蛋白建立大鼠AR模型,C组用生理盐水代替卵清蛋白。然后A组以鼻内类固醇激素喷鼻,B、C组以生理盐水代替。末次激发后观察动物鼻部症状和体征,并取鼻黏膜行苏木精-伊红染色计数鼻黏膜内嗜酸粒细胞(EOS)数,阿辛蓝-过碘酸-希夫染色观察杯状细胞变化,扫描电镜下观察各组鼻黏膜超微结构的改变。结果:鼻内类固醇激素能明显减轻AR鼻部症状,其评分与B组差异有统计学意义(P<0.01);其鼻腔黏膜内EOS数和杯状细胞数明显降低,与B组相比差异有统计学意义(P<0.01),而与C组差异无统计学意义(P>0.05);扫描电镜检查结果显示A组鼻黏膜纤毛结构与C组相似,而B组纤毛倒伏、排列紊乱、缠绕集结、大量分泌物附着等。结论:鼻内类固醇激素能明显缓解AR症状及鼻黏膜炎性反应状态,并对受损纤毛有明显修复作用。     

A study of some current methods for assessment of nasal histamine reactivity

The aim of this study was to investigate the reactivity of the nasal mucosa of patients with pollen allergy compared to healthy controls, when challenged with histamine outside the pollen season. Assessments were made with symptom score, acoustic rhinometry, nasal peak expiratory and inspiratory flow (NPEF and NPIF) and rhinomanometry in order to find the most sensitive method for the purpose. Twenty-one patients with seasonal allergic rhinitis and 20 healthy controls were challenged with histamine dihydrochloride in increasing concentrations (0.01, 0.1, 1.0 mg/ml) locally in the nose. Our results show no difference in mucosal reactivity between the patients and controls regardless of the method used. When comparing the methods we find that NPIF and NPEF are more sensitive to mucosal changes than the other methods we have studied.     

鼻腔冲洗治疗变应性鼻炎的疗效观察

目的：比较鼻腔冲洗及鼻用激素治疗对变应性鼻炎（AR）患者鼻部症状及气道炎症相关指标的影响,探讨鼻腔冲洗在AR治疗中的意义。方法：将61例经变应原皮肤点刺试验诊断为AR的患者随机分为3组：A组17例（单纯鼻用激素治疗）,B组21例（单纯鼻腔冲洗）,C组23例（鼻腔冲洗联合鼻用激素）。观察各组治疗前、治疗3个月后鼻部症状视觉模拟量表（VAS）评分和鼻炎结膜炎生活质量（RQLQ）评分及下气道呼出气一氧化氮（FENO）值。结果：3组患者治疗前VAS、RQLQ评分及FENO值比较差异无统计学意义（P〉0.05）,具有可比性。治疗3个月后3组患者VAS、RQLQ评分及FENO值均明显降低（P〈0.05）。治疗3个月后3项指标减少差值比较,VAS、RQLQ评分3组间差异无统计学意义,FENO值A、C组与B组比较均差异有统计学意义（均P〈0.05）。结论：鼻腔冲洗能改善AR患者的鼻部症状,提高患者的生活质量,降低下气道炎症。鼻腔冲洗治疗AR有效,与鼻用激素联合使用能取得更明显的效果。     

Radiofrequency for the treatment of allergic rhinitis refractory to medical therapy

OBJECTIVES/HYPOTHESIS: The ideal treatment for allergic rhinitis refractory to medical therapy is still lacking. The aim of the study is to evaluate the efficacy of turbinate surgery with radiofrequency for the treatment of allergic rhinitis that is unresponsive to medical therapy. STUDY DESIGN: A prospective, nonrandomized clinical study. METHODS: From February 2000 to April 2002, 108 consecutive patients (45 men and 63 women [mean age, 29.5 y]) with allergic rhinitis refractory to medical therapy who underwent radiofrequency turbinate surgery were enrolled in the study. Postoperative follow-up ranged from 12 to 26 months. A standard 0-to-10 visual analogue scale with an anchor was used to assess the pain and the allergic symptoms, including nasal obstruction, rhinorrhea, sneezing, itchy nose, and itchy eyes, preoperatively and postoperatively at the end of weeks 1 and 2 and months 1, 3, 6, and 12 after surgery. Statistical analysis was determined by repeated measures of ANOVA. RESULTS: None of the 108 patients had obvious discomfort other than mild numbness over the premaxillary area (24 of 108 [22.2%]) during operation. Also, no adverse reactions including bleeding, infection, adhesion, or a worsening of allergic symptoms were encountered. One hundred one patients were included in the final statistical analysis. Only nine patients reported no improvement at all after treatment. The response rate of radiofrequency turbinate surgery for allergic rhinitis refractory to medical therapy was 91.1% (92 of 101). At 1 year after the treatment, the degree of nasal obstruction had changed on the visual analogue scale (mean +/- SD) from 6.84 +/- 2.09 to 2.47 +/- 1.60, an improvement of 63.9%. The degree of rhinorrhea had changed from 5.74 +/- 2.75 to 2.57 +/- 2.31, an improvement of 55.2%. The degree of sneezing had changed from 5.30 +/- 2.80 to 2.59 +/- 2.13, an improvement of 51.1%. The degree of itchy nose had changed from 3.74 +/- 3.16 to 1.82 +/- 2.27, an improvement of 51.3%. The degree of itchy eyes had changed from 3.17 +/- 3.09 to 1.68 +/- 2.38, an improvement of 47.0%. The visual analogue scale scores for nasal obstruction, rhinorrhea, sneezing, itchy nose, and itchy eyes decreased significantly with time, from preoperative scores to scores at 1 year after surgery. Other additional effects and improvements, including headache, lumpy throat, night cough, and tinnitus, were also reported by the patients. Most of the patients stated that they would consider repeating this procedure if necessary and would recommend the new method to their friends with the same problems. CONCLUSIONS: The study demonstrates that radiofrequency appears to be an effective and safe tool for treating allergic rhinitis with poor response to medical therapy. In the future, radiofrequency has the potential to be one of the most popular surgical modalities for the treatment of allergic rhinitis refractory to medical therapy.     

Posture-induced nasal obstruction in patients with allergic rhinitis

Nasal resistance is affected by posture. In this study, the effects of supine and lateral recumbent positions were investigated in eight normal subjects and 31 patients with allergic rhinitis. Of the 31 patients with allergic rhinitis, five showed unilateral complete nasal obstruction and one patient showed bilateral complete obstruction during the change of posture. Total nasal resistance had a tendency to increase with repeating the change of posture (a paired t-test, P < 0.05). The supine and lateral recumbent positions did not induce variable changes in total nasal resistance in normal subjects. Posture induces complete nasal obstruction in the supine or lateral recumbent positions in some patients with allergic rhinitis.     

The prevalence of allergic rhinitis and nasal symptoms in Nottingham

From 1200 households selected at random, 2114 questionnaires were returned from individuals over 14 years old. They reported that in the previous year the prevalence of ‘symptoms of nasal obstruction every day for more than 14 consecutive days’ was 16.9%; 19.8% had had a ‘runny nose’; 7.1% reported sneezing bouts; and 19.6% had hay fever during the same period. Also, 13.7% had had rhinosinusitis in the previous year using the criterion of ‘two out of three symptoms of congestion, rhinorrhoea and sneezing for more than 1 h per day for a period in excess of 2 weeks’. The prevalence of perennial symptoms in individuals who did not have hay fever was 8.6%. Over the previous 2 years 18.2% of all respondents had visited their General Practitioner and 0.2% had visited a hospital as a result of their hay fever. Individuals who responded as having hay fever were significantly more likely to have worked in an environment with a lot of dust in the last 2 years than asymptomatic respondents (χ², P= 0.002), although fume exposure was not found to be a significant risk factor (P= 0.0681). Individuals with perennial symptoms were no more likely to have been working in a dusty or smoky environment. In those with either seasonal or perennial symptoms there was no significant effect of either social class or manual/nonmanual occupation.     

Changes in nasal mucosal blood flux and air-flow resistance on unilateral histamine challenge

To investigate reflex vascular control in the nose, we challenged each side of the nose with 0.9% saline and histamine (0.3 mg aqueous) and observed changes in unilateral nasal airway resistance (Rnaw) and laser doppler flux (LDF) in response to contra-lateral and ipsilateral challenge in eight normal subjects. Preliminary studies demonstrated that the preferred site for observation of LDF was the nasal septum (same-day concordance 0.920; inferior turbinate 0.307). Ipsilateral contra-lateral saline induced no significant change to either parameter. Ipsilateral histamine produced a highly significant rise in LDF (757 arbitrary units sem 94 at 3 min; baseline 489 sem 75: P < 0.05) and Rnaw (baseline: 3.10, sem 0.52; 5min: 8.81, sem 2.09 cmH₂O/1/s: P < 0.01). Contra-lateral histamine produced a significant P < 0.05) fall in both (LDF 317, sem 24 at 3 min; Rnaw 2.67, sem 0.78 cm H₂O/1/s at 6 min). This previously unrecorded observation suggests a neural reflex that increases the patency of the contralateral nostril after unilateteral obstruction is provoked.     

Effects of beclomethasone dipropionate nasal spray on subjective and objective findings in perennial allergic rhinitis

Effects of beclomethasone dipropionate nasal spray on subjective and objective findings in perennial allergic rhinitis It was the aim of this trial to study the effect of intranasal beclomethasone dipropionate on symptoms and signs of perennial allergic rhinitis in Japanese patients. In a multicenter trial 183 patients, children and adults, were treated with placebo or with 400 μgbeclomethasone dipropionate a day for 2 weeks. The active treatment had an effect on all nasal symptoms: sneezing, nose blowing, and blockage being reduced to 34%, 44% and 63% (P <0 01) of the values in the placebo group. A considerable carry-over effect was found, suggesting a group comparative design to be preferable for a cross over trial for the study of intranasal steroids. The beclomethasone dipropionate therapy had a significant inhibitory effect on the immediate response to nasal allergen provocation. The number of secretion eosinophils was reduced during treatment, and the appearance of the mucous membrane tended to normalize. Local side effects were few and insignificant. It is concluded that beclomethasone dipropionate is a valuable drug for the treatment of perennial allergic rhinitis.     

变应性因素及变应性鼻炎与慢性鼻-鼻窦炎鼻息肉的相关性探讨

目的：探讨变应性因素及变应性鼻炎（AR）与慢性鼻-鼻窦炎鼻息肉的临床相关性。方法：将200例研究对象分为A、B组,A组诊断为AR（110例）,B组诊断为慢性鼻-鼻窦炎鼻息肉（90例）,通过欧蒙印迹法定量检测血清sIgE浓度并观察慢性鼻-鼻窦炎鼻息肉手术治疗后的复发率、AR并发慢性鼻-鼻窦炎鼻息肉的发生率。结果：A组sIgE总阳性率为89.09%,B组sIgE总阳性率为74.44%。B组中sIgE阳性者术后复发率为58.21%,sIgE阴性者术后复发率为8.70%。A组41例（37.27%）并发慢性鼻-鼻窦炎鼻息肉,血清sIgE阳性率为97.56%;69例（62.73%）未并发慢性鼻-鼻窦炎鼻息肉,血清sIgE阳性率为79.71%;组内slgE阳性率比较差异有统计学意义（χ2=6.96,P〈0.01）。结论：变应性因素及AR与慢性鼻-鼻窦炎鼻息肉的发生有一定的相关性,提示避免接触变应原、合理治疗AR能够有效控制慢性鼻-鼻窦炎鼻息肉的复发率。     

变应性鼻炎大鼠鼻黏膜纤毛超微结构和鼻症状变化的研究

目的:通过变应原诱发大鼠变应性鼻炎(AR),观察鼻黏膜纤毛超微结构和鼻腔症状变化的特点。方法:采用卵清蛋白(OVA)为变应原激发大鼠鼻黏膜建立AR大鼠模型,建模成功后,每周2次鼻腔激发,分别至16 d、42 d、56 d、112 d、140 d。正常对照组在整个试验过程中以生理盐水代替OVA。观察变应原激发后的鼻黏膜纤毛超微结构改变以及检测鼻黏膜中浸润的嗜酸粒细胞(EOS)情况,同时观察变应原诱导的大鼠鼻腔流涕症状。结果:暴露变应原会引起大鼠鼻黏膜细胞纤毛排列紊乱,有的纤毛粘集成团向不同方向倾倒,上皮纤毛和绒毛多数脱落等超微结构进行性损害改变,EOS浸润先增多后降低;抓鼻次数变化无统计学意义,而鼻腔流涕症状起初一直加重,随着暴露变应原时间的延长出现鼻涕排除障碍。结论:AR大鼠模型在延长变应原诱导下鼻黏膜纤毛呈进行性损害;此外,长期变应原攻击下鼻腔症状变化可能与鼻黏膜纤毛结构进行性损害有关。     

Eotaxin在变应性鼻炎中的表达及组胺调控作用的研究

目的：通过变应性鼻炎动物模型了解Eotaxin在变应性鼻炎中的表达以及变态反应炎性递质组胺对Eotaxin表达的影响,以期深入了解变应性鼻炎的发病机制。方法：卵蛋白致敏法建立变应性鼻炎大鼠模型,应用免疫组织化学、RT-PCR及ELISA法,观察组胺及组胺HR1拮抗剂干预后鼻黏膜、血清及鼻腔灌洗液中Eotaxin的表达量或含量变化。结果：变应性鼻炎干预组与变应性鼻炎无干预组相比,鼻腔灌洗液以及鼻黏膜中Eotaxin的表达量较前者显著增加（P〈0.05）,而H1拮抗剂干预组血清、鼻腔灌洗液以及鼻黏膜中Eotaxin增加均显著受到抑制（P〈0.05）。结论：本实验进一步确认了Eotaxin参与了变应性鼻炎发病的理论基础。组胺作为一种变应性鼻炎中的重要炎症递质可以通过影响Eotaxin的表达参与变应性鼻炎的发病过程,且HR1亦参与了这一过程。     

2种手术方法治疗伴鼻中隔偏曲的变应性鼻炎的疗效分析

目的：观察2种手术方法治疗伴鼻中隔偏曲的变应性鼻炎的疗效及应用价值。方法：将87例伴鼻中隔偏曲的变应性鼻炎患者根据下鼻甲黏膜肥厚及骨增生情况分为2组,分别行鼻中隔偏曲矫正联合双下鼻甲低温等离子射频消融并骨折外移术、鼻中隔偏曲矫正联合双下鼻甲骨黏膜下部分切除术,疗效采用2004兰州标准和鼻阻力测量值进行评价。结果：术后随访1年,患者鼻阻力较术前明显改善,2组症状改善的总有效率均大于88%。结论：2种手术方法均显著降低了患者的鼻阻力,改善了过敏性症状,效果良好。     

Ho:YAG laser treatment of hyperplastic inferior nasal turbinates.

OBJECTIVES: Although preliminary studies about the successful use of the Ho:YAG laser in nasal turbinate surgery have been reported, no clinical study has been performed on this procedure. The aim of this prospective clinical study was to assess the long-term effect of Ho:YAG laser in the treatment of hyperplastic inferior nasal turbinates. METHODS: Eighty-five patients with nasal obstruction who did not respond to conservative medical treatment were treated with a pulsed Ho:YAG laser (wavelength of =2080 nm). Fifty-two of these patients were included in this clinical study and were followed for 1 year. RESULTS: Within the first 2 weeks, nasal obstruction was correlated to the extent of nasal crusting. Six months after laser treatment, the mucociliary function test showed no variation compared with the preoperative measurements. One year after laser treatment 77% of the patients demonstrated improved nasal airflow on rhinomanometry and questionnaire. CONCLUSIONS: Ho:YAG-laser treatment of hyperplastic turbinates can be performed as outpatient surgery under local anesthesia and offers controllable ablation of soft tissue in a short operation time with satisfactory results and excellent patient acceptance.