多组分免疫营养补充剂用于过敏性哮喘和鼻炎患儿的探索性先导试验：INAPRA研究
2026/06/30
摘要
背景：过敏性哮喘和过敏性鼻炎（AR）是儿童期最常见的慢性疾病之一。二者常在儿童中共存，其病理基础为2型驱动的气道炎症以及上皮-免疫相互作用受损。免疫营养和后生元策略已被提出作为这些疾病的辅助治疗方法。本研究旨在探讨含后生元的多组分免疫营养补充剂对合并过敏性哮喘和AR儿童的临床及免疫调节潜力。
方法：儿童呼吸道过敏免疫营养（INAPRA）研究是一项多中心、随机、双盲、安慰剂对照的探索性先导试验。40例5～12岁、对屋尘螨（Dermatophagoides pteronyssinus）致敏且合并哮喘和AR的儿童按1∶1随机分组，每日接受多组分补充剂［丁酸钠、热灭活鼠李糖乳杆菌GG、低聚果糖、维生素D3、二十二碳六烯酸、槲皮素和紫苏（Perilla frutescens）提取物］或安慰剂，持续6个月。共同主要结局为采用儿童哮喘控制测试（c-ACT）、儿童版哮喘与过敏性鼻炎控制测试（CARATkids）和鼻部症状总评分（TNSS）评估的呼吸道症状控制变化。次要结局包括外周血单个核细胞（PBMC）中的细胞因子产生、调节性T细胞比例以及耐受相关基因（gfb1、Ptgs2、Csf2和Ifna2）表达。采用干预前采集的PBMC进行体外免疫学检测。
结果：两组基线临床特征相当。经基线校正后分析显示，在3项预设症状控制指标中，接受研究产品的儿童6个月结局均优于安慰剂组。c-ACT的校正后组间差异为4.625分（95% CI：3.705～5.545；p＜0.001），TNSS的校正后组间差异为-3.960分（95% CI：-4.890～-3.030；p＜0.001）。CARATkids存在显著的治疗与基线交互作用；在平均基线评分水平，校正后的条件性组间差异为-7.019分（95% CI：-8.143～-5.895；p＜0.001）。安慰剂组使用缓解药物更多。研究期间未报告与研究产品相关或无关的不良事件，依从性超过90%。体外实验显示，与研究产品共孵育可减弱过敏原诱导的Th2细胞因子（IL-4、IL-5、IL-13）分泌，增加IL-10产生，提高CD4+CD25+FoxP3+调节性T细胞比例，并上调Tgfb1、Ptgs2、Csf2和Ifna2的表达。
结论：在这项探索性先导随机对照试验中，补充多组分免疫营养制剂6个月与儿童过敏性哮喘和鼻炎控制改善相关。临床改善与对免疫细胞的有益调节作用相一致。
Exploratory pilot trial of a multicomponent immunonutritional supplement in children with allergic asthma and rhinitis: The INAPRA study
Erika Caldaria, Raffaele Iorio, Dario Marziali, Franca Oglio, Alessia Cadavere, Antonio Masino, Alessandra Agizza, Serena Coppola, Laura Carucci
Abstract
BACKGROUND:Allergic asthma and allergic rhinitis (AR) are among the most frequent chronic conditions in the pediatric age. They frequently coexist in children and are sustained by type 2-driven airway inflammation and impaired epithelial-immune interactions. Immunonutritional and postbiotic strategies have been proposed as adjunctive therapeutic approaches for these diseases. To explore the clinical and immunomodulatory potential of a multicomponent immunonutritional supplement containing postbiotics in children with concomitant allergic asthma and AR.
METHODS:The ImmuneNutrition Against Pediatric Respiratory Allergies (INAPRA) study was a multicenter, randomized, double-blind, placebo-controlled exploratory pilot trial. Forty children aged 5-12 years with asthma and AR sensitized to Dermatophagoides pteronyssinus were randomized (1:1) to receive a daily multicomponent supplement (sodium butyrate, heat-inactivated L. rhamnosus GG, fructooligosaccharides, vitamin D3, docosahexaenoic acid, quercetin, and Perilla frutescens extract) or placebo for 6 months. Co-primary outcomes were changes in respiratory symptom control assessed by Childhood Asthma Control Test (c-ACT), CARATkids, and Total Nasal Symptom Score (TNSS). Secondary outcomes included cytokine production, regulatory T-cell rate and tolerogenic gene expression (gfb1, Ptgs2, Csf2, and Ifna2) in peripheral blood mononuclear cells (PBMCs). Immunological assays were performed in vitro on PBMCs collected before intervention.
RESULTS:Baseline clinical characteristics were comparable between groups. In baseline-adjusted analyses, children receiving the study product showed more favorable 6-month outcomes than those receiving placebo across all three prespecified symptom-control measures. The adjusted between-group difference was 4.625 points (95% CI 3.705 to 5.545; p < 0.001) for c-ACT and -3.960 points (95% CI -4.890 to -3.030; p < 0.001) for TNSS. For CARATkids, a significant treatment-by-baseline interaction was detected; at the mean baseline score, the adjusted conditional between-group difference was -7.019 points (95% CI -8.143 to -5.895; p < 0.001). The use of rescue medications was higher in the placebo group. No adverse events related or unrelated to the study product were reported, and adherence exceeded 90%. In in vitro experiments, co-incubation with the study product attenuated allergen-induced Th2 cytokine secretion (IL-4, IL-5, IL-13), increased IL-10 production, enhanced CD4+CD25+FoxP3+ regulatory T-cell rate, and upregulated Tgfb1, Ptgs2, Csf2, and Ifna2 expression.
CONCLUSION:In this exploratory pilot RCT, six-month supplementation with a multicomponent immunonutritional formulation was associated with improvement of allergic asthma and rhinitis control in children. The clinical improvement paralleled with beneficial modulatory actions in immune cells.
背景：过敏性哮喘和过敏性鼻炎（AR）是儿童期最常见的慢性疾病之一。二者常在儿童中共存，其病理基础为2型驱动的气道炎症以及上皮-免疫相互作用受损。免疫营养和后生元策略已被提出作为这些疾病的辅助治疗方法。本研究旨在探讨含后生元的多组分免疫营养补充剂对合并过敏性哮喘和AR儿童的临床及免疫调节潜力。
方法：儿童呼吸道过敏免疫营养（INAPRA）研究是一项多中心、随机、双盲、安慰剂对照的探索性先导试验。40例5～12岁、对屋尘螨（Dermatophagoides pteronyssinus）致敏且合并哮喘和AR的儿童按1∶1随机分组，每日接受多组分补充剂［丁酸钠、热灭活鼠李糖乳杆菌GG、低聚果糖、维生素D3、二十二碳六烯酸、槲皮素和紫苏（Perilla frutescens）提取物］或安慰剂，持续6个月。共同主要结局为采用儿童哮喘控制测试（c-ACT）、儿童版哮喘与过敏性鼻炎控制测试（CARATkids）和鼻部症状总评分（TNSS）评估的呼吸道症状控制变化。次要结局包括外周血单个核细胞（PBMC）中的细胞因子产生、调节性T细胞比例以及耐受相关基因（gfb1、Ptgs2、Csf2和Ifna2）表达。采用干预前采集的PBMC进行体外免疫学检测。
结果：两组基线临床特征相当。经基线校正后分析显示，在3项预设症状控制指标中，接受研究产品的儿童6个月结局均优于安慰剂组。c-ACT的校正后组间差异为4.625分（95% CI：3.705～5.545；p＜0.001），TNSS的校正后组间差异为-3.960分（95% CI：-4.890～-3.030；p＜0.001）。CARATkids存在显著的治疗与基线交互作用；在平均基线评分水平，校正后的条件性组间差异为-7.019分（95% CI：-8.143～-5.895；p＜0.001）。安慰剂组使用缓解药物更多。研究期间未报告与研究产品相关或无关的不良事件，依从性超过90%。体外实验显示，与研究产品共孵育可减弱过敏原诱导的Th2细胞因子（IL-4、IL-5、IL-13）分泌，增加IL-10产生，提高CD4+CD25+FoxP3+调节性T细胞比例，并上调Tgfb1、Ptgs2、Csf2和Ifna2的表达。
结论：在这项探索性先导随机对照试验中，补充多组分免疫营养制剂6个月与儿童过敏性哮喘和鼻炎控制改善相关。临床改善与对免疫细胞的有益调节作用相一致。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（Int Immunopharmacol. 2026 Sep;184:116903. DOI: https://doi.org/10.1016/j.intimp.2026.116903）
（Int Immunopharmacol. 2026 Sep;184:116903. DOI: https://doi.org/10.1016/j.intimp.2026.116903）
Exploratory pilot trial of a multicomponent immunonutritional supplement in children with allergic asthma and rhinitis: The INAPRA study
Erika Caldaria, Raffaele Iorio, Dario Marziali, Franca Oglio, Alessia Cadavere, Antonio Masino, Alessandra Agizza, Serena Coppola, Laura Carucci
Abstract
BACKGROUND:Allergic asthma and allergic rhinitis (AR) are among the most frequent chronic conditions in the pediatric age. They frequently coexist in children and are sustained by type 2-driven airway inflammation and impaired epithelial-immune interactions. Immunonutritional and postbiotic strategies have been proposed as adjunctive therapeutic approaches for these diseases. To explore the clinical and immunomodulatory potential of a multicomponent immunonutritional supplement containing postbiotics in children with concomitant allergic asthma and AR.
METHODS:The ImmuneNutrition Against Pediatric Respiratory Allergies (INAPRA) study was a multicenter, randomized, double-blind, placebo-controlled exploratory pilot trial. Forty children aged 5-12 years with asthma and AR sensitized to Dermatophagoides pteronyssinus were randomized (1:1) to receive a daily multicomponent supplement (sodium butyrate, heat-inactivated L. rhamnosus GG, fructooligosaccharides, vitamin D3, docosahexaenoic acid, quercetin, and Perilla frutescens extract) or placebo for 6 months. Co-primary outcomes were changes in respiratory symptom control assessed by Childhood Asthma Control Test (c-ACT), CARATkids, and Total Nasal Symptom Score (TNSS). Secondary outcomes included cytokine production, regulatory T-cell rate and tolerogenic gene expression (gfb1, Ptgs2, Csf2, and Ifna2) in peripheral blood mononuclear cells (PBMCs). Immunological assays were performed in vitro on PBMCs collected before intervention.
RESULTS:Baseline clinical characteristics were comparable between groups. In baseline-adjusted analyses, children receiving the study product showed more favorable 6-month outcomes than those receiving placebo across all three prespecified symptom-control measures. The adjusted between-group difference was 4.625 points (95% CI 3.705 to 5.545; p < 0.001) for c-ACT and -3.960 points (95% CI -4.890 to -3.030; p < 0.001) for TNSS. For CARATkids, a significant treatment-by-baseline interaction was detected; at the mean baseline score, the adjusted conditional between-group difference was -7.019 points (95% CI -8.143 to -5.895; p < 0.001). The use of rescue medications was higher in the placebo group. No adverse events related or unrelated to the study product were reported, and adherence exceeded 90%. In in vitro experiments, co-incubation with the study product attenuated allergen-induced Th2 cytokine secretion (IL-4, IL-5, IL-13), increased IL-10 production, enhanced CD4+CD25+FoxP3+ regulatory T-cell rate, and upregulated Tgfb1, Ptgs2, Csf2, and Ifna2 expression.
CONCLUSION:In this exploratory pilot RCT, six-month supplementation with a multicomponent immunonutritional formulation was associated with improvement of allergic asthma and rhinitis control in children. The clinical improvement paralleled with beneficial modulatory actions in immune cells.
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