耐受性指导的剂量调整在儿童尘螨诱导变应性鼻炎舌下免疫治疗中的应用：一项为期6个月的前瞻性队列研究

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中文摘要

背景： 舌下免疫治疗（SLIT）对变应性鼻炎（AR）有效，但其疗效存在个体间差异且呈剂量依赖性。标准化方案可能无法在所有儿科患者中达到最佳结局，这凸显了个体化剂量调整策略的必要性。鼻变应原激发试验（NAC）是评估鼻黏膜反应性的金标准，为评估治疗反应和指导剂量个体化提供了客观工具。
目的： 评估个体化SLIT剂量调整对尘螨诱导AR儿童的短期（6个月）疗效，并评估其对上下气道炎症和肺功能的影响。
方法： 在这项前瞻性队列研究中，235名（3-14岁）尘螨诱导AR儿童被分配至标准剂量组（SD，n=133）或剂量调整组（DA，n=102）。DA组根据耐受性逐步增加维持剂量（最高至效价No.4的7滴）。在基线和6个月后评估结局，包括症状和药物评分（TNSS、TMS、CSMS、VAS、RQLQ）、NAC反应性、肺功能（FEV₁ Z评分）、呼出气一氧化氮分数（FeNO）和鼻一氧化氮（nNO）。两组基线特征总体均衡，但年龄和病程除外，已在多变量分析中加以校正。
结果： 6个月后，两组所有症状评分均显著改善（均P<0.001），在校正年龄和病程后，DA组改善更大（TNSS：B=-0.648，95% CI：-1.186至-0.109，P=0.019；TMS：B=-0.141，95% CI：-0.184至-0.098，P<0.001；CSMS：B=-0.304，95% CI：-0.448至-0.161，P<0.001；VAS：B=-0.893，95% CI：-1.295至-0.490，P<0.001；RQLQ：B=-1.282，95% CI：-2.152至-0.413，P=0.004）。DA组中NAC反应性降低的患者比例更高（校正OR=1.67，95% CI：1.01-2.75，P=0.046）。两组FeNO和nNO均显著降低（均P<0.05）。DA组FEV₁ Z评分较基线也显著增加（平均变化=0.725，95% CI：0.299-1.150，d=0.822，P=0.002），且该值显著高于SD组（平均差=0.872，95% CI：0.138-1.605，d=0.714，P=0.021）。
结论： 在这项前瞻性儿科队列中，基于耐受性的个体化SLIT剂量调整与更好的短期结局、降低的鼻黏膜反应性和改善的肺功能相关。这些发现支持耐受性指导剂量个体化的可行性，并值得在随机对照试验中加以证实。

英文摘要

BACKGROUND: Sublingual immunotherapy (SLIT) is effective for allergic rhinitis (AR), though its efficacy exhibits inter-individual variability and is dose-dependent. Standardized protocols may not achieve optimal outcomes in all pediatric patients, highlighting the need for individualized dose-adjustment strategies. The nasal allergen challenge (NAC), the gold standard for assessing nasal mucosal reactivity, provides an objective tool to evaluate treatment response and guide dose personalization.
OBJECTIVE: To evaluate the short-term (6-month) efficacy of individualized SLIT dose adjustment in children with dust mite-induced AR, and to assess its effects on upper and lower airway inflammation and lung function.
METHODS: In this prospective cohort study, 235 children (3-14 years) with dust mite-induced AR were assigned to a standard-dose group (SD, n = 133) or a dose-adjustment group (DA, n = 102). The DA group received an incrementally increased maintenance dose based on tolerance (up to 7 drops of potency No. 4). Outcomes were assessed at baseline and after 6 months, including symptom and medication scores (TNSS, TMS, CSMS, VAS, RQLQ), NAC reactivity, lung function (FEV₁ Z-score), fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO). Baseline characteristics were generally balanced between groups, except for age and disease duration, which were adjusted for in multivariable analyses.
RESULTS: After 6 months, all symptom scores improved significantly in both groups (all P < 0.001), with greater improvement in the DA group after adjusting for age and disease duration (TNSS: B = -0.648, 95% CI: -1.186 to -0.109, P = 0.019; TMS: B = -0.141, 95% CI: -0.184 to -0.098, P < 0.001; CSMS: B = -0.304, 95% CI: -0.448 to -0.161, P < 0.001; VAS: B = -0.893, 95% CI: -1.295 to -0.490, P < 0.001; RQLQ: B = -1.282, 95% CI: -2.152 to -0.413, P = 0.004). A higher proportion of patients in the DA group showed reduced NAC reactivity (adjusted OR = 1.67, 95% CI: 1.01-2.75, P = 0.046). Both groups exhibited significant reductions in FeNO and nNO (all P < 0.05). The DA group also showed a significant increase in FEV₁ Z-score from baseline (mean change = 0.725, 95% CI: 0.299-1.150, d = 0.822, P = 0.002), and the value was significantly higher than that in the SD group (mean difference = 0.872, 95% CI: 0.138-1.605, d = 0.714, P = 0.021).
CONCLUSION: In this prospective pediatric cohort, individualized SLIT dose adjustment based on tolerance was associated with better short-term outcomes, reduced nasal mucosal reactivity, and improved lung function. These findings support the feasibility of tolerance-guided dose personalization and warrant confirmation in randomized controlled trials.