[Efficacy comparison and safety analysis of subcutaneous specific immunotherapy with standardized house dust mite allergen in patients with single and multiple allergic rhinitis].

Objective: To investigate the efficacy and safety of house dust mite (HDM) allergen subcutaneous specific immunotherapy (SCIT) in patients with allergic rhinitis (AR) with single dust mite allergy and multiple allergen allergy. Methods: A retrospective study was conducted. A total of 372 patients with allergic rhinitis induced by house dust mite were diagnosed in the allergy clinic of General Hospital of North Theater Command from January 2013 to January 2018.They were treated with house dust mite allergen preparation for standardized SCIT for 3 years or more, and had complete follow-up data. The age ranged from 5 to 55 years, the median age was 13 years, and the average age was (19.4±14.7) years; 216 males and 156 females. According to their age, they were divided into the older group (age >14 years) and younger group (age ≤ 14 years). According to the number of allergens, they were divided into single group (only HDM group allergic to house dust mites) and multi recombination (including 2 or more allergens including house dust mites). The multi recombination was further divided into HDM+1 group, HDM+2 group, HDM+3 group, HDM+4 and above group. Before treatment (T0), 1 year (T1) and 3 years (T2) after SCIT treatment, the patients in each group established files, analyzed and compared the average total nasal symptoms score (TNSS), total non nasal symptoms score (TNNSS), visual analogue scale (VAS), total medicine score (TMS) and rhinoconjunctivitis quality of life questionnaire (RQLQ), and evaluated the clinical efficacy of the treatment and the comparison of various scores in the efficacy of SCIT with different allergens and ages. Record the occurrence of local and systemic adverse reactions of all patients during treatment, and evaluate the safety of SCIT. All scores are measurement data that do not conform to normal distribution. Mann-Whitney U and Kruskai-Wallis test of independent samples are used for inter group comparison, and Bonferroni correction is used for further pairwise comparison; Chi square test and continuity correction method were used for the comparison between count data groups such as the incidence of adverse reactions and the effective rate of TNSS, and a-division method was used for further pairwise comparison. Results: After SCIT treatment, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in T1 and T2 were significantly lower than those in T0, and the scores in T2 were significantly lower than those in T1 (Z=-11.168, -4.786, -6.639, -13.012, -10.652 in T0 vs T1; Z=-13.527, -8.746, -13.397, -14.477, -11.833 in T0 vs T2; Z=-4.721, -4.607, -10.020, -7.180, -5.721 in T1 vs T2; P<0.05). In T1 and T2, compared with the older group, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in younger group were lower, and the differences of various indexes were statistically significant(the median scores of T1: Myounger=3.0, 1.0, 2.0, 4.0, 2.6, Molder=5.0, 2.0, 3.0, 5.0, 3.2; the median scores of T2: Myounger=3.0, 1.0, 0, 2.0, 1.3, Molder=4.0, 1.0, 1.5, 3.0, 2.3; ZT1=-4.525, -5.830, -4.061, -3.608, -2.785; ZT2=-3.847, -4.055, -2.820, -2.998, -3.418; P<0.05). In T1 and T2, the scores of TNSS, VAS and RQLQ in a single group after SCIT treatment were lower than those in multiple recombination(the median scores of T1:Msingle=4.0, 4.0, 2.6, Mmultiple=5.0, 5.0, 3.2; the median scores of T2: Msingle=3.0, 2.0, 1.4, Mmultiple=4.0, 3.0, 2.1), and the difference was statistically significant (ZT1=-3.002, -2.092, -1.977; ZT2=-3.354, -2.469, -2.116; P<0.05). There was no significant difference in TMS (the median score during T1 period: Msingle=2.0, Mmultiple=3.0, ZT1=-1.130; the median score during T2 period: Msingle=1.0, Mmultiple=1.0, ZT2=-1.544; P>0.05). Further comparison within the group showed that there was no significant difference in the improvement rate of TNSS during T2 period among HDM group, HDM+1 group, HDM+2 group and HDM+3 group (HDM vs HDM+1 group χ2=0.277, HDM vs HDM+2 group χ2=0.78, HDM vs HDM+3 group χ2=0.075, HDM+1 vs HDM+2 group χ2=0.057, HDM+1 vs HDM+3 group χ2=0.019, HDM+2 vs HDM+3 group χ2=0.003; P>0.005), the improvement rates were 92.5%, 90.3%, 89.1% and 89.5%. Respectively in HDM group,HDM+1 group, HDM+2 group, HDM+3 group, compared with HDM+4 and above group, the difference was statistically significant (χ2=26.144, 13.254, 15.144, 8.808; P<0.005). The improvement rate of TNSS in HDM+4 and above group was 60.9%. 122 patients had local adverse reactions during the treatment of SCIT, accounting for 32.8%. The local adverse reactions were 759 injections (15 336 injections in total), accounting for 4.95%. Most of them were swelling, dizziness, induration and pruritus at the injection site, which could be relieved by oral antihistamines or within 2 hours. There were 2 cases of local urticaria, once for each case. The symptoms were relieved within 1 week after oral antihistamine. No serious systemic adverse reactions occurred. Conclusion: Standardized SCIT may be a safe and effective treatment for AR patients, and the type of allergen may be one of the important factors affecting the efficacy of SCIT. The efficacy of SCIT was significant in AR patients with three or less allergens other than house dust mite.目的： 探讨屋尘螨（house dust mite，HDM）变应原皮下特异性免疫治疗（subcutaneous specific immunotherapy，SCIT）对单一尘螨过敏和多重变应原过敏的变应性鼻炎（allergic rhinitis，AR）患者的疗效比较及安全性评估。 方法： 回顾性研究，选择2013年1月至2018年1月就诊于北部战区总医院呼吸内科变态反应门诊，确诊为HDM诱发的变应性鼻炎并应用屋尘螨变应原制剂进行3年及以上标准化SCIT，且有完整随访资料患者共372例进行分析，年龄5~55岁、中位数年龄13岁、（19.4±14.7）岁；男性216例，女性156例；根据年龄将其分为高龄组（>14岁）和低龄组（≤14岁）；根据过敏原数量将其分为单一过敏原组（仅对屋尘螨过敏的HDM组）和多重过敏原组（包含尘螨在内2种或2种以上过敏原），多重过敏原组再分为HDM+1组、HDM+2组、HDM+3组、HDM+4及以上组。各组患者在治疗前（T0期）、接受SCIT治疗1年时（T1期）和3年时（T2期）建立档案，分析比较平均鼻炎症状评分（TNSS）、鼻炎伴随症状评分（TNNSS）、视觉模拟评分（VAS）、总用药评分（TMS）及鼻结膜炎生活质量问卷（RQLQ），评估此疗法的临床疗效以及不同变应原谱、年龄对于SCIT疗效中各项评分的比较。记录治疗期间所有患者局部及全身不良反应的发生情况，评估SCIT的安全性。各项评分均为不符合正态分布的计量资料，组间比较采用Mann-Whitney U和独立样本Kruskai-Wallis检验，进一步两两比较选用Bonferroni校正；不良反应发生率及TNSS有效率等计数资料组间比较时选用χ²检验和连续性校正法，进一步两两比较选用α分割法校正。 结果： 372例患者SCIT治疗后T1期与T2期的TNSS、TNNSS、TMS、VAS、RQLQ评分均较T0期明显减少，T2期各项评分较T1期明显减少，差异均有统计学意义（T0 vs T1期比较Z=-11.168、-4.786、-6.639、-13.012、-10.652；T0 vs T2期比较Z=-13.527、-8.746、-13.397、-14.477、-11.833；T1 vs T2期比较Z=-4.721、-4.604、-10.020、-7.180、-5.721；均P<0.05）。在T1期与T2期，与高龄组相比，低龄组TNSS、TNNSS、TMS、VAS、RQLQ评分均较低，各指标比较差异均有统计学意义（T1期的各项评分中位数分别为M低龄组=3.0、1.0、2.0、4.0、2.6，M高龄组=5.0、2.0、3.0、5.0、3.2；T2期各项评分中位数分别为：M低龄组=3.0、1.0、0、2.0、1.3，M高龄组=4.0、1.0、1.5、3.0、2.3；T1期的Z=-4.525、-5.830、-4.061、-3.608、-2.785；T2期的Z=-3.847、-4.055、-2.820、-2.998、-3.418；均P<0.05）。在T1期与T2期，单一组SCIT治疗后TNSS、VAS及RQLQ评分均低于多重组（T1期的各项评分中位数分别为M单一组=4.0、4.0、2.6，M多重组=5.0、5.0、3.2；T2期各项评分中位数分别为：M单一组=3.0、2.0、1.4，M多重组=4.0、3.0、2.1），差异均有统计学意义（T1期的Z=-3.002、-2.092、-1.977；T2期的Z=-3.354、-2.469、-2.116；P均<0.05），TMS比较差异无统计学意义（T1期的评分中位数M单一组=2.0、M多重组=3.0，Z=-1.130；T2期的评分中位数M单一组=1.0、M多重组=1.0，Z=-1.544；均P>0.05）。进一步组内两两比较发现，T2期HDM组、HDM+1组、HDM+2组、HDM+3组TNSS改善率组间比较差异均无统计学意义（HDM vs HDM+1比较χ2=0.277、HDM vs HDM+2比较χ2=0.785、HDM vs HDM+3比较χ2=0.075、HDM+1 vs HDM+2比较χ2=0.057、HDM+1 vs HDM+3比较χ2=0.019、HDM+2 vs HDM+3比较χ2=0.003；均P>0.005），改善率分别为92.5%、90.3%、89.1%及89.5%，而HDM+4及以上组TNSS改善率为60.9%，分别与HDM+4及以上组比较差异均有统计学意义（χ2=26.144、13.254、15.144、8.808；均P<0.005）。所有患者SCIT治疗注射期间发生局部不良反应122例，占总人数32.8%；局部不良反应共759针次（总注射针次15 336次），占比4.95%，大部分以注射部位肿胀、红晕、硬结、瘙痒为主，口服抗组胺药物或2 h内可自行缓解；其中有2例出现局部荨麻疹，每例各1次，口服抗组胺药物后1周内症状缓解；无严重全身不良反应发生。 结论： 标准化SCIT对于AR患者可能是一种安全有效的治疗方案，过敏原种类可能是SCIT疗效的重要影响因素之一；合并除屋尘螨以外的其他3种及3种以下过敏原的AR患者，SCIT疗效比较显著。.