【作者】 刘丽萍；

【导师】 董亮；

【作者基本信息】 山东大学 ， 临床医学（内科学·呼吸病学）（专业学位）， 2016， 博士

【摘要】 背景全世界范围内变应性鼻炎及变应性哮喘的发病率呈逐年上升的趋势,花粉及尘螨是引起变应性鼻炎及变应性哮喘的最常见变应原。我国已有多项调查研究显示花粉和尘螨亦是我国变应性疾病常见的变应原,其比例占所有变应原的60%以上。目前已有少数几项关于不同变应原的变应性鼻炎在流行病学、病因学及病理学上异同点的研究,也有少数几项关于不同变应原在变应性鼻炎发展为变应性哮喘自然病程中的作用的研究,另外还有几项关于变应原的敏感程度与变应性疾病病情严重程度相关性的研究。这些研究由于研究方法,筛选的人群、疾病严重程度评估标准及地域和季节性的差异,导致不同的结果和结论。变应原的研究应考虑地域性和季节性的差异,因此本研究的目的就是调查中国东部沿海地区单纯尘螨过敏或单纯花粉过敏的哮喘患者临床流行病学资料特点,以期对当地哮喘个体化、具体化防治方案提供科学依据。目的调查中国东部沿海地区不同变应原致敏哮喘患者的临床资料特征,并对不同致敏原哮喘患者病情严重程度进行比较分析。材料与方法这是一个横断面的流行病学调查研究,2011年7月至2014年1月就诊于我院变态反应科门诊的单纯花粉过敏或单纯尘螨过敏的哮喘患者共239例符合入选标准纳入研究,其中共199名患者进行了血清总1gE及血常规检测。根据不同点致敏变应原分成2组：花粉组、螨虫组。由门诊专科医师或护师通过一对一、面对面填写门诊哮喘患者档案的形式,对患者临床资料进行收集。内容包括：患者居住情况；既往症状诱发因素；既往治疗；症状好发时间及季节；变应性鼻炎及哮喘首次发病年龄；个人过敏史：如湿疹史、变应性鼻炎及变应性结膜炎史、皮肤过敏史、药物食物过敏史；家族性过敏性疾病史；变应性鼻炎的症状及对生活、工作和学习的影响；临床用药情况。通过门诊随访治疗6个月后填写哮喘控制测试问卷(ACT),对哮喘的控制情况进行调查,并通过哮喘控制所需药物情况,对患者哮喘病情的严重程度进行评估。结果1.花粉组中农村居民的比例明显增高,而螨虫组中居民类型无明显差异。2.花粉组和螨虫组中约84.9%的患者同时合并变应性鼻炎,两组间变应性鼻炎发病率无明显差异；花粉组中变应性结膜炎的发病率明显高于螨虫组；螨虫组中哮喘患者2岁后湿疹的发病率明显高于花粉组,但两组中急性荨麻疹的发病率无明显差异；两组中食物过敏和药物过敏的情况无明显差异。螨虫组中血清总T1gE的水平明显高于花粉组,而两组间血清嗜酸性粒细胞计数水平无明显差异。3.两组哮喘患者中有家族过敏性疾病史占71.1%,且单独父系一方有过敏性疾病史的占41.4%,明显高于母系一方21.3%,且差异具有统计学意义。两组间比较无明显差异。4.花粉组患者变应性鼻炎的首次发病年龄均数为27.7±13.7,哮喘的首次发病年龄均数为30.5±15.62,比变应性鼻炎的平均发病年龄晚3年；16～45岁是花粉组患者变应性鼻炎及哮喘的好发年龄。螨虫组患者变应性鼻炎的首次发病年龄均数为19.79±12.49,哮喘的首次发病年龄均数为19.03±11.63,与哮喘变应性鼻炎的平均发病年龄无明显差异；1-44岁是螨虫组患者变应性鼻炎及哮喘的好发年龄。螨虫组变应性鼻炎及哮喘的首次发病年龄均早于花粉组,无论花粉组还是螨虫组变应性鼻炎和哮喘的首次发病在高龄组均较低。5.单纯花粉致敏的变应性鼻炎患者,中/重度鼻炎的比例明显高于螨虫组；单纯尘螨致敏的哮喘患者,中/重度哮喘的比例明显高于花粉组。结论我们研究发现不同变应原哮喘患者具有某些不同或者相同的临床特征：如不同的居住环境影响着致敏变应原的种类；不同的合并症(变应性结膜炎、湿疹史)；不同的发病年龄及不同的变应性疾病自然进程；不同的疾病严重程度；相同的变应性鼻炎发病率、相同的食物及药物过敏发病率,以及相同的家族性过敏性疾病史。背景慢性气道炎症及气道重塑是支气管哮喘主要特征。既往曾认为气道重塑是长期气道炎症的结果,近期研究显示气道炎症和气道重塑是同步发生的,即气道重塑可以发生在哮喘发病的早期,因此在控制哮喘的治疗中,在治疗气道炎症的同时也应该注意抑制气道重塑的发生。最新研究发现高分辨率CT作为一种无创的检查方法其空间分辨率高,能够准确有效的评估肺组织及支气管形态结构的改变,一些CT相关的检测指标可用来评估哮喘患者的气道壁厚度,能够评估哮喘的气道重构程度。变应性哮喘是最常见的支气管哮喘表型,该种类型的哮喘患者常因接触一种或多种气传变应原,如尘螨、花粉、动物皮屑或真菌等诱发或加重,变应原在哮喘的发生、发展过程中起着非常重要的作用。历史研究数据显示花粉和尘螨这两种常见的变应原在诱发哮喘发作和加重的机制上,相关的炎症细胞及炎症介质及哮喘患者的临床特征上存在某些相同点和不同点。历史上,花粉变应原是否能诱发哮喘发作曾存在争议。也有学者研究认为在哮喘的发生发展中,相对于室外过敏原(如花粉)室内过敏原(如尘螨)作用更重要些。据我们所知目前没有关于不同变应原的变应性哮喘患者气道壁厚度即气道重塑情况的对比性研究报道。因此本研究主要运用高分辨率CT评估不同变应原哮喘患者气道壁的厚度,对支气管哮喘的个体化、具体化防治方案提供科学依据。目的运用高分辨CT评估单纯花粉过敏或单尘螨过敏的哮喘患者气道壁厚度,并对不同变应原哮喘患者肺功能指标进行比较。材料与方法85位重度支气管哮喘患者根据变应原检测结果分成花粉组和螨虫组。20位健康志愿者作为对照组。用高分辨CT测量入选者右肺上叶尖端支气管起始端支气管横截总面积(WT)和支气管官腔面积(LA),则支气管管壁面积(WA)=WT-LA,并计算支气管管壁面积占支气管横截总面积的百分数(WA%),所有检测指标以体表面积(BSA)进行标准化纠正。同时对入选者肺功能指标进行分析比较。结果(1) WA/BSA、WA%和FEF25-75% pred值花粉组较螨虫组差异有统计学意义,尤其是WA/BSA,螨虫组明显高于花粉组(p<0.01),关于FEV1%pred、FEV1/FVC and LA/BSA值,两组间无明显差异。(2)我们发现在花粉组中,支气管管壁面积与哮喘患者的鼻炎病程相关(r=0.351,p<0.05),而与患者哮喘病程无明显相关性(r=0.322,p=0.056)；而在螨虫组我们发现支气管管壁面积及管腔面积与哮喘患者的哮喘病程相关,而与患者的变应性鼻炎病程无明显相关性。(3)花粉组中FEV1/FVC与WA%呈弱的负相关(r=-0.335,p=0.046),而在螨虫组FEV1/FVC与WA%呈明显的正相关,而与LA/BSA呈负相关(r=-0.289,p=0.044)。(4)在花粉组FEV1/FVC和FEF25-75% pred与变应性鼻炎的病程呈负相关(r=-0.477, p=0.003; r=-0.378, p=0.023).(5)健康对照组FEV1/FVC和FEF25-75% pred值明显高于哮喘组,而WA/BSA和LA/BSA值明显低于哮喘组。FEV1和WA%值健康对照组和哮喘组无明显差异。结论单纯花粉致敏和单纯尘螨致敏的哮喘患者气道壁的厚度存在差异,小气道通气功能指标亦存在差异。更多还原

【Abstract】 BackgroundThroughout the world there is an upward trend in the incidence of allergic diseases, allergic asthma and allergic rhinitis is the most common allergic diseases. More researchers found that house dust mites and pollen were the most common allergen to allergic rhinitis and allergic asthma. In china, numbers of researches have shown that pollen and mites also are the important and common allergens to allergic disease, the percentage accounted for more than 60% of all allergens. At present there were few study about the clinical profile and therapeutic strategies in patients for allergic rhinitis caused by grass pollen or house-dust mite, and the correlation between sensitizations and severity of allergic diseases is controversial.We can found that the conclusion is different from each studies, because of the different genetic and sociocultural populations, different area, different season and different ways of survey. There are very few studies which analyzed the characteristics of allergic asthma according to the profiles of sensitization to different allergens in china. So the purpose of this study is to research the characteristics of asthma patients with house dust mite allergy or pollen allergy in China’s eastern coastal areas.ObjectiveThe purpose of this study was to investigate the characteristics of asthma patients with mono-sensitized to weed pollen or house dust mite in China’s eastern coastal areas.Methods239 asthma patients came from our outpatient clinic from July 2011 to March 2014 were divided into pollen group and mite group according to their sensitization to significant allergens.All information about the demographic characteristics, personal and family history of allergic diseases, the time of first attack of rhinitis and asthma and the impact of allergic rhinitis and asthma on daily activities, work or school, night-time sleep and the medications for controlling the symptomswas were collected through the form of questionnaire. Serum total lgE and Eosinophil were detected at the same time.Results1. There are no obvious difference between pollen group and mite group in patient’s age and gender. More patients with grass pollen allergy had been living rural area than urban area.2. The serum total TlgE level of mite group was obviously higher than that of pollen group (p= 0.033), while there were no obvious difference about the serum eosinophil count between the two groups. About 84.9% of the patients overall merged with allergic rhinitis, there was no difference between the two groups; the proportion of allergic conjunctivitis and atopic dermatitis in the two group was significant different, and the incidence of acute urticarial, Food allergy and drug allergy in the two groups was no significant difference.3. About 71.1% asthma patients had a family history of allergic disease, interestingly, the proportion of paternal side history of allergy disease was more highly than that of maternal side, and the difference is statistically significant.There was no obvious difference between the two groups.4. The age range for the first attack of rhinitis and asthma in the mite group is similar; it is 3 years for the first attack of asthma later than the first attack of rhinitis in pollen group.5. There air most patients with moderate/severe rhinitis were in pollen group, and most patients with moderate/severe asthma were in mite group.ConclusionsThere are same or different clinical features for allergic asthma due to mono-sensitized to different allergens, such as different living environment affects the type of main allergens, different complications (allergic conjunctivitis and dermatitis), different natural course from rhinitis to asthma, different degree of severity and control of rhinitis and asthma, and same incidence of allergic rhinitis, food allergy and drug allergy. Same familial history of allergic disease.BackgroundAsthma is characterized by chronic airway inflammation and remodeling of airway, the latter is usually shown airway wall thickening, High-resolution computed tomography have been defined and proposed as useful tool for evaluating airway wall thickness. Allergic asthma is often triggered by two common airborne allergens:dust mite and weed pollen. Data coming from histological studies have shown that the two allergens are different but also similar in the pathogenesis of triggering asthma attacks or exacerbations、inflammatory cells and mediators and clinical features. Some authors concluded that Sensitization to dust mite is generally more important than sensitization to weed pollen for the development of asthma. Patients with weed pollen allergy will need longer time of development of asthma. some searchers ever thought that pollens had little important contribution to the pathogenesis of asthma, To the best of our knowledge, there were few studies which explored the difference in airway wall thickness of allergic asthma with sensitization to different allergens. So the aim of this study was to compare the airway wall thickness using HRCT and the pulmonary function between asthma patients with dust mite allergy or weed pollen allergy.ObjectiveTo explore the possible difference of airway wall thickness of asthma patients mono-sensitized to weed pollen or dust mite using high-resolution computed tomography.Methods85 severe asthma patients were divided into weed pollen group and dust mite group according to relevant allergen.20 healthy donors served as controls. Airway wall area, percentage wall area and luminal area at the trunk of the apical bronchus of the right upper lobe were quantified using HRCT and compared. The values of pulmonary function were assessed as well.ResultsThere were differences between dust mite group and weed pollen group in WA/BSA,WA% and FEF25-75% pred, and no significant difference in FEV1%pred、 FEV1/FVC and LA/BSA. In weed pollen group, WA/BSA was observed to correlate with the duration of rhinitis, whereas in dust mite group, WA/BSA and LA/BSA was observed to correlate with the duration of asthma. In weed pollen group, FEV1/FVC showed a weak but significant negative correlation with WA%, but in dust mite group FEV1/FVC showed a significant positive correlation with WA% and a statistical negative correlation with LA/BSA. FEV1/FVC and FEF25-75% pred were higher and WA/BSA and LA/BSA were lower in healthy control group than asthma group. FEV1%pred and WA% was no significant difference between asthma patients and healthy subjects.ConclusionsThere are differences between dust mite mono-sensitized asthma patients and weed pollen mono-sensitized asthma patients, not only in airway wall thickness, but also small airway obstruction.更多还原