中国医科大学学报  2023, Vol. 52 Issue (12): 1119-1124

文章信息

洪志军, 李锐, 姜涛, 赵迪, 鹿伟理, 李宪华, 曹志伟
HONG Zhijun, LI Rui, JIANG Tao, ZHAO Di, LU Weili, LI Xianhua, CAO Zhiwei
大连市尘螨过敏变应性鼻炎患者变应原谱分析
Analysis of allergen profiles in dust mite-sensitive allergic rhinitis patients in Dalian
中国医科大学学报, 2023, 52(12): 1119-1124
Journal of China Medical University, 2023, 52(12): 1119-1124

文章历史

收稿日期:2023-07-12
网络出版时间:2023-12-06 16:16:51
大连市尘螨过敏变应性鼻炎患者变应原谱分析
洪志军1 , 李锐2 , 姜涛2 , 赵迪2 , 鹿伟理2 , 李宪华2 , 曹志伟3     
1. 大连医科附属第一医院健康管理中心,辽宁 大连 116021;
2. 大连大学附属中山医院耳鼻咽喉科,辽宁 大连 116001;
3. 中国医科大学附属盛京医院耳鼻咽喉科,沈阳 110004
摘要目的 分析大连市尘螨过敏变应性鼻炎患者变应原谱分布情况,为变应性鼻炎的精准防控奠定基础。方法 收集2015年1月至2022年12月大连大学附属中山医院就诊的变应性鼻炎患者的临床资料。按照性别、年龄、变应原检出情况及反应级别、合并其他过敏原情况及检测时间分组,比较不同组间变应原谱分布情况。结果 共纳入1 330例,其中尘螨过敏总检出率为60.83% (809/1330),单纯尘螨致敏330例(40.79%),多重致敏479例(59.21%)。多重致敏者变应原谱种类繁多,尘螨基础上合并了20种变应原,其中合并致敏前三位的变应原依次为艾蒿、猫毛和普通豚草,合计占64.52% (522/809)。尘螨合并1~3种变应原居多,占88.73% (425/479),最多同时合并10种变应原。合并1~3种变应原中以吸入性变应原为主,合并≥4种变应原均为吸入与食物性变应原。变应原反应级别分析显示,尘螨致敏反应较为强烈,≥3级占61.19% (495/809),其他合并变应原除艾蒿外,致敏反应以1级、2级为主。男性、女性尘螨过敏检出率分别为61.84%、59.94%,男女比较无统计学差异(χ2=4.000,P = 0.261)。< 20岁年龄组尘螨过敏检出率最高,而且随年龄增长尘螨过敏检出率下降(χ2=69.984,P < 0.001)。尘螨过敏变应性鼻炎主要在8~10月份发生,10月份尘螨检出率最高,达80.16%。结论 大连市尘螨过敏变应性鼻炎发生率较高,多重致敏多见,以合并1~3种吸入性变应原为主,艾蒿、猫毛和普通豚草是尘螨最常合并的变应原。因此应针对本地区尘螨过敏特点重点防控。
关键词变应性鼻炎    尘螨过敏    变应原    
Analysis of allergen profiles in dust mite-sensitive allergic rhinitis patients in Dalian
1. The Health Management Center, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China;
2. Department of Otolaryngology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China;
3. Department of Otolaryngology, Shengjing Hospital of China Medical University, Shenyang 110004, China
Abstract: Objective To investigate the allergen profiles of dust mite-sensitive allergic rhinitis patients in Dalian, and to lay the foundation for precise prevention and control of allergic rhinitis. Methods Clinical data of allergic rhinitis patients treated at Affiliated Zhongshan Hospital of Dalian University from January 2015 to December 2022 were collected. The allergen distribution spectrums were compared between different groups designated according to sex, age, allergen reaction level, combination of other allergens, and testing time. Results A total of 1 330 allergic rhinitis patients were included, among whom the total detection rate of dust mite allergy was 60.83% (n = 809), with 330 (40.79%) of these having dust mite sensitization alone and 479 (59.21%) having multiple sensitization. There were many kinds of allergens in multiple sensitization. Among those with dust mite allergy, all 20 combined allergens detected in this group were analyzed, and mugwort, cat hair, and common rinea grass were the top three allergens in combined sensitization, accounting for 64.52%. The number of other allergens combined with dust mite was mainly 1-3 species (88.73%), and a maximum of 10 allergens were simultaneously present. Patients with 1-3 other combined sensitivities were mainly reactive to respiratory allergens, and those with 4 or more allergens essentially had joint sensitization to respiratory and food allergens. As for the allergen reaction level, the dust mite sensitivity reaction was relatively strong, with grade 3 or above accounting for 61.19%. Except for mugwort, the other combined allergens elicited mainly grade 1 and grade 2 reactions. The detection rates of dust mite allergy were 61.84% in male patients and 59.94% in female patients, with no statistical difference between the sexes (χ2=4.000, P = 0.261). The detection rate of dust mite sensitization was highest in the group aged < 20 years and decreased with age (χ2=69.984, P < 0.001). Dust mite-sensitive allergic rhinitis mainly occurred from August to October, and the detection rate of dust mite sensitization was the highest in October, reaching 80.16%. Conclusion The dust mite sensitization rate in patients with allergic rhinitis in the Dalian area is relatively high, and multiple sensitization is more common. Combinations of respiratory allergens mainly involve 1-3 types, and mugwort, cat hair, and common ragweed are the most common allergens combined with dust mite. Therefore, prevention and control of allergic rhinitis should focus on the characteristics of dust mite allergy in this region.
Keywords: allergic rhinitis    dust mite    allergen    

变应性鼻炎(allergic rhinitis,AR) 是机体暴露于变应原后主要由IgE介导的鼻黏膜非感染性慢性炎症疾病。尘螨是AR、哮喘和特应性皮炎等的主要致敏原及病因[1]。本团队以往研究[2-4]发现尘螨是大连市AR患者的首位变应原,较早开展了针对尘螨过敏AR的特异性免疫治疗。然而,AR患者变应原多样,往往合并其他变应原。因此,进一步分析尘螨过敏AR患者的过敏原谱及临床特点对AR的精准防控及治疗尤为重要。目前,关于尘螨过敏AR变应原谱分析鲜有报道,本研究收集我院近年来尘螨过敏AR患者的临床资料,分析尘螨过敏AR患者的变应原谱情况,旨在为本地区AR的防治提供参考和依据。

1 材料与方法 1.1 临床资料

收集2015年1月至2022年12月大连大学附属中山医院耳鼻咽喉科AR患者的临床资料。纳入标准:(1) AR确诊符合《中国变应性鼻炎诊断和治疗指南(2022年,修订版) 》 [5]诊断标准;(2) 完成血清特异性IgE抗体检测;(3) 大连市常住人口(居住5年及以上);(4) 临床资料完整。将尘螨≥1级的AR患者认定为尘螨过敏AR[5]。本研究获得大连大学附属中山医院伦理委员会批准(2021031)。

1.2 变应原检测

采用过敏原特异性IgE抗体检测试剂盒(德国欧蒙公司) 检测变应原,利用EUROLineScan软件判定结果。检测项目包括:柳树/杨树/榆树、普通豚草、艾蒿、屋尘螨/粉尘螨、屋尘、猫毛、狗毛、蟑螂、点青霉/分支孢霉/烟曲霉、啤酒花、蛋清、牛奶、花生、大豆、牛肉、羊肉、海洋鱼组合、淡水鱼组合、虾、螃蟹。致敏反应分级标准[6]:0级,< 0.35 kU/L;1级,0.35~ < 0.7 kU/L;2级,0.7~ < 3.5 kU/L;3级,3.5~ < 17.5 kU/L;4级,17.5~ < 50 kU/L;5级,50~ < 100 kU/L;6级,≥100 kU/L。

1.3 统计学分析

采用SPSS 23.0软件进行统计分析,计数资料采用率(%) 表示,组间比较采用χ2检验或者Fisher确切概率法,P < 0.05为差异有统计学意义。

2 结果 2.1 一般资料统计结果

共纳入1 330例,平均年龄(25.51±14.19) 岁;尘螨过敏809例(60.83%),平均年龄(22.90±14.90) 岁。尘螨过敏AR中,男384例(61.84%,384/621),女425例(59.94%,425/709),男女尘螨过敏发病率比较差异无统计学意义(χ2=4.000,P = 0.261)。不同年龄组间尘螨过敏发病率比较差异有统计学意义(χ2=69.984,P < 0.001),而且随年龄增长尘螨过敏发病率逐渐下降,见表 1

表 1 尘螨过敏AR患者年龄分布 Tab.1 Age distribution of AR patients with dust mite allergy
Group AR Dust mite allergy [n (%)]
< 10 years 264 197 (74.62)
10-< 20 years 239 174 (72.80)
20-< 30 years 289 161 (55.71)
30-< 40 years 315 178 (56.51)
40-< 50 years 137 67 (48.91)
50-< 60 years 66 26 (39.39)
≥60 years 20 6 (30.00)

2.2 尘螨过敏AR患者变应原谱及致敏分级情况

结果显示,20种变应原均有尘螨过敏AR患者检测出来。合并人数较多的变应原依次是艾蒿、猫毛和普通豚草,均为吸入性变应原,三者合计共522例,占64.52%。而合并人数较少的变应原为羊肉、花生和牛肉,均为食物性变应原,三者合计共32例,占3.96%。

变应原致敏反应分级结果显示,尘螨1~5级患者较多,6级患者较少。其中3级患者最多,3~5级患者495例,占61.19%。尘螨合并的变应原中,致敏反应1、2级居多,仅艾蒿存在6级致敏反应;而且随着致敏反应级别增高各变应原所致AR患者数量呈现减少趋势,见表 2

表 2 尘螨过敏AR患者变应原谱及致敏反应分级情况[n (%)] Tab.2 Allergen spectrum and reaction levels of AR patients with dust mite sensitivity[n (%)]
Allergen n Allergen reaction level
1 2 3 4 5 6
House dust mites/dust mites 809 174 (21.51) 130 (16.07) 206 (25.46) 180 (22.25) 109 (13.47) 10 (1.24)
Mugwort 282 52 (18.44) 49 (17.38) 58 (20.57) 56 (19.86) 51 (18.09) 16 (5.67)
Cat hair 158 57 (27.08) 37 (23.42) 31 (19.62) 23 (14.56) 10 (6.33) 0 (0.00)
Common ragweed 82 47 (57.32) 14 (17.07) 15 (18.29) 2 (2.44) 4 (4.88) 0 (0.00)
House dust 59 43 (72.88) 8 (13.56) 4 (6.78) 4 (6.78) 0 (0.00) 0 (0.00)
Crab 41 23 (56.10) 9 (21.95) 6 (14.63) 3 (7.32) 0 (0.00) 0 (0.00)
Egg white 39 27 (69.23) 11 (28.21) 0 (0.00) 0 (0.00) 1 (2.56) 0 (0.00)
Dog hair 37 11 (29.73) 11 (29.73) 10 (27.03) 4 (10.81) 1 (2.70) 0 (0.00)
Willow/poplar /elm 35 23 (65.71) 9 (25.71) 3 (8.57) 0 (0.00) 0 (0.00) 0 (0.00)
Soybean 32 17 (53.13) 11 (34.38) 2 (6.25) 2 (6.25) 0 (0.00) 0 (0.00)
Cockroach 31 24 (77.42) 6 (19.35) 1 (3.23) 0 (0.00) 0 (0.00) 0 (0.00)
Ocean fish combination 29 17 (58.62) 6 (20.69) 6 (20.69) 0 (0.00) 0 (0.00) 0 (0.00)
Milk 27 23 (85.19) 4 (14.81) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00)
Penicillium spot/sporade/aspergillus fumigatus 26 17 (65.38) 7 (26.92) 2 (7.69) 0 (0.00) 0 (0.00) 0 (0.00)
Freshwater fish combination 23 13 (56.52) 6 (26.09) 3 (13.04) 1 (4.35) 0 (0.00) 0 (0.00)
Humulus lupulus 19 13 (68.42) 2 (10.53) 4 (21.05) 0 (0.00) 0 (0.00) 0 (0.00)
Shrimp 15 7 (46.67) 3 (20.00) 4 (26.67) 1 (6.67) 0 (0.00) 0 (0.00)
Beef 11 8 (72.73) 3 (27.27) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00)
Peanut 11 8 (72.73) 3 (27.27) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00)
Mutton 10 5 (50.00) 0 (0.00) 3 (30.00) 2 (20.00) 0 (0.00) 0 (0.00)

2.3 尘螨过敏AR患者合并其他变应原情况

结果显示,多重致敏患者共479例。其中合并1种变应原患者(231例) 最多、其次依次为2种(120例) 及3种(74例),最多同时合并10种变应原。合并1~3种变应原患者共425例,占88.73%;变应原主要为吸入性变应原。合并4种及以上多为吸入性变应原与食物。合并1种变应原中,艾蒿患病人数最多,占45.89% (106/231),其次为猫毛19.48% (45/231) 及屋尘5.19% (12/231)。合并2种变应原中,以艾蒿、普通豚草25.83% (31/120) 及艾蒿、猫毛20.83% (25/120) 患病人数居多。合并3种及以上变应原中,多为艾蒿和猫毛或者艾蒿和普通豚草基础上合并其他变应原,另外发现多重致敏者患者数量随着合并变应原种类增加而逐渐减少。见表 3

表 3 尘螨过敏AR患者合并其他变应原情况 Tab.3 Distribution of allergens combined with dust mite in AR patients
Quantity and type of combined allergens* n The percent age (%)
1 kind (n = 231)
  Mugwort 106 45.89
  Cat hair 45 19.48
  House dust 12 5.19
2 kinds (n = 120)
  Mugwort,common ragweed 31 25.83
  Mugwort,cat hair 25 20.83
  Mugwort,house dust 9 7.50
  House dust,cat hair 9 7.50
3 kinds (n = 74)
  Mugwort,cat hair,common ragweed 8 10.81
  Mugwort,cat hair,house dust 7 9.46
  Mugwort,common ragweed,beef 4 5.41
4 kinds (n = 26)
  Mugwort,cat hair,common ragweed,soybean 2 7.69
  Mugwort,cat hair,milk,humulus lupulus 2 7.69
  Mugwort,crab,shrimp,cockroach 2 7.69
5 kinds (n = 11)
  Mugwort,common ragweed,ocean fish combination,beef,peanut 1 9.09
  Mugwort,common ragweed,freshwater fish combination,house dust,cockroach 1 9.09
  Mugwort,common ragweed,cat hair,ocean fish combination,beef 1 9.09
6 kinds (n = 9)
  Mugwort,common ragweed,crab,beef,soybean,freshwater fish combination 1 11.11
  Mugwort,common ragweed,crab,ocean fish combination,beef,egg white 1 11.11
  Mugwort,common ragweed,cat hair,willow/poplar /elm,milk,egg white 1 11.11
7 kinds (n = 5)
  Mugwort,common ragweed,cat hair,house dust,beef,soybean,peanut 1 20.00
  Mugwort,common ragweed,cat hair,willow/poplar /elm,milk,beef,egg white 1 20.00
  Mugwort,common ragweed,cat hair,willow/poplar /elm,beef,egg white,penicillium spot/spo- rade/ aspergillus fumigatus 1 20.00
8 kinds (n = 2)
  Mugwort,common ragweed,milk,soybean,shrimp,crab,beef,peanut 1 50.00
  Cat hair,crab,milk,soybean,shrimp,ocean fish combination,egg white,peanut 1 50.00
10 kinds (n = 1)
  House dust,willow/poplar/elm,ocean fish combination,mutton,milk,beef,shrimp,egg white,peanut,freshwater fish combination 1 100.00
*,only the top three combined were listed.

2.4 不同性别及年龄组尘螨过敏AR患者合并其他变应原致敏情况

结果显示,单纯尘螨致敏患者330例(40.79%),多重致敏者479例(59.21%),男性AR者中多重致敏者占62.50% (240/384),女性AR者中多重致敏者占56.24% (239/425),二者比较无统计学差异(χ2=3.287,P = 0.070)。不同年龄组间单纯尘螨致敏及多重致敏者比较有统计学差异(χ2=22.774,P = 0.001)。见表 4

表 4 单纯尘螨过敏及合并其他变应原AR患者的性别及年龄分布[n (%)] Tab.4 Distributions of sex and age between simple dust mite allergen group and dust mite combined with other allergens group [n (%)]
Group n Simple dust mite group Dust mite combined with other allergens group
Sex
  Male 384 144 (37.50) 240 (62.50)
  Female 425 186 (43.76) 239 (56.24)
Age
   < 10 years 197 78 (39.59) 119 (60.41)
  10-< 20 years 174 60 (34.98) 114 (65.52)
  20-< 30 years 161 55 (34.16) 106 (65.84)
  30-< 40 years 178 98 (55.06) 80 (44.94)
  40-< 50 years 67 28 (41.79) 39 (58.21)
  50-< 60 years 26 8 (30.77) 18 (69.23)
  ≥60 years 6 2 (33.33) 4 (66.67)
Total 809 330 (40.79) 479 (59.21)

2.5 尘螨过敏AR发病时间分布

结果显示,尘螨过敏AR发病(55.25%,447/809) 与AR发病(56.99%,758/1 330) 时间基本一致,均集中在8~10月份。每月尘螨过敏AR检出率均较高,为50.00%~80.16%;以10月份最高,为80.16%,见图 1

图 1 尘螨过敏AR患者发病时间分布 Fig.1 Distribution of time of AR occurrence in patients with dust mite allergy

3 讨论

早在1964年,尘螨就被证明是室内的主要变应原[7]。陆续有研究发现,粉尘螨和屋尘螨是引起人类变态反应性疾病的两种最常见尘螨[8];尘螨粪便颗粒是屋尘变应原的主要来源,Der p1、Der p2和Der p23是尘螨的主要致敏原[9]。大连市属于沿海地区,气候湿润,更利于尘螨的生长与繁殖。因此,尘螨是大连市变应性疾病的重要致病因素,并已被多个研究证实为大连市主要致敏原[2, 10-11]。另外,多项研究[12-13]显示我国变应性疾病的致敏原为两种或两种以上并存。随着全球变应性疾病发病率逐年升高,变应原在临床诊断和特异性免疫治疗中意义重大[14]

本研究AR中尘螨致敏高达60.83%,与张樊苹等[11] 同区域研究结果(63.94%) 一致,高于谷娅楠等[10]的研究结果(42.20%),也高于刘天夫等[15]鞍山市研究结果(46.39%)。此外,本研究单纯尘螨致敏及尘螨合并其他变应原致敏发生率男女比较无统计学差异(P > 0.05),但不同年龄组间有统计学差异(P < 0.05)。尘螨过敏在 < 20岁年龄组发生率(> 70%) 高,并随年龄增长尘螨过敏发生率逐渐降低,提示尘螨是大连市青少年AR的防控重点。除30~ < 40岁组外,其他各年龄组多重致敏率均较高,提示其他变应原在AR的发病中也发挥重要作用,因此,全面检测变应原谱对AR患者的精准防控十分重要。

多重致敏患者会出现多个系统症状,从而使患者生活质量下降。因此,多重致敏成为AR防控的难点及重点。2023年,我国一项关于华北地区屋尘螨过敏成分血清学分析研究[16]结果显示,多种变应原致敏增加了过敏性哮喘的风险。多重致敏分为交叉致敏和共同致敏,交叉致敏是特异性抗体或细胞受体对两种不同的变应原(致敏蛋白组分) 均能产生应答;序列同源性超过70%可发生交叉反应,越接近的物种,发生交叉反应的概率越大[17-18]。而共同致敏指对2种及2种以上变应原同时致敏,且IgE抗体识别2种及2种以上变应原不同表达;这些变应原不需要共同的结构特征也可以同时结合到相应变应原IgE抗体[18-19]。本研究59.21%的尘螨致敏AR患者是与其他变应原共存的多重致敏状态,40.79%患者为单纯尘螨致敏,与刘天夫等[15]多重致敏(58.79%) 及单尘螨致敏(41.21%) 的研究结果一致。

本研究还发现多重致敏患者的变应原谱种类繁多,尘螨基础上合并了检测的20种变应原。其中艾蒿(34.86%)、猫毛(19.13%) 和普通豚草(10.14%) 患者所占比例最大。合并其他变应原数量分析结果显示,以合并1~3种变应原为主(88.73%),最多合并了10种变应原;合并1~3种变应原中多为吸入性变应原,合并≥4种变应原多为吸入性与食物变应原。变应原致敏反应分级结果显示,尘螨致敏反应较强烈,≥3级占61.19% (495/809);除艾蒿外,其他变应原致敏反应多为1级、2级。因此,尘螨是大连市AR防控的重点。

已有研究[20]表明,尘螨过敏有季节变化特点。美国北部尘螨过敏多出现在潮湿的夏季,而干燥的冬季较少发生[21]。本研究结果显示,8~10月份是大连市尘螨过敏AR的高发季节,其中10月最高,占80.16%。分析原因可能是不同地区气候条件不同导致了变应原致敏反应发生的时间不同。因此,气候也是AR防控需要考虑的重要因素。

综上所述,大连市尘螨过敏AR发生率较高,多重致敏多见,以合并1~3种吸入性变应原为主,艾蒿、猫毛和普通豚草是尘螨最常合并的变应原。因此应针对本地区尘螨过敏特点重点防控。本研究样本来源局限,仅为1所医院;患者资料不全面,尚缺少职业、家族史及疾病史等内容。今后需联合多家医疗机构,扩大样本量进一步论证。

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