Pediatrics · Medical Literature
Exploratory pilot trial of a multicomponent immunonutritional supplement in children with allergic asthma and rhinitis: The INAPRA study.
Abstract
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. 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. 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. 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. ClinicalTrials.gov Identifier NCT07308288.
Clinical relevance
In children aged 5–12 years with concomitant allergic asthma and allergic rhinitis sensitized to Dermatophagoides pteronyssinus, does a 6-month daily multicomponent immunonutritional supplement (containing sodium butyrate, heat-inactivated Lactobacillus rhamnosus GG, fructooligosaccharides, vitamin D3, DHA, quercetin, and Perilla frutescens extract) improve respiratory symptom control and immunological biomarkers compared with placebo? __SNAPSHOT__ {"studyDesign":"Multicenter, randomized, double-blind, placebo-controlled exploratory pilot trial","setting":"Not reported (multicenter; presumed Italian pediatric allergy centers based on authorship and supplement composition context)","sampleSize":"n=40 (intervention: 20, control: 20; 1:1 allocation)","population":"Children aged 5–12 years with physician-diagnosed concomitant allergic asthma and allergic rhinitis, sensitized to Dermatophagoides pteronyssinus","intervention":"Daily oral multicomponent immunonutritional supplement containing sodium butyrate, heat-inactivated Lacticaseibacillus rhamnosus GG (postbiotic), fructooligosaccharides (prebiotic), vitamin D3, docosahexaenoic acid (DHA), quercetin, and Perilla frutescens extract for 6 months","comparator":"Matched placebo administered daily for 6 months","primaryOutcome":"Co-primary outcomes: changes in respiratory symptom control assessed by the Childhood Asthma Control Test (c-ACT), CARATkids, and Total Nasal Symptom Score (TNSS; abstract truncated — additional co-primary outcomes not reported in the excerpt provided)","followUp":"6 months (treatment duration); post-treatment follow-up duration not reported in the available abstract","fundingSource":"Not reported"}
Key findings
The abstract provided to the reviewer is truncated after the description of co-primary outcomes (c-ACT, CARATkids, Total N[asal Symptom Score]); no quantitative results — including between-group differences, absolute or relative effect sizes, confidence intervals, p-values, or secondary immunological outcome data — are available from the excerpt supplied. Accordingly, no efficacy or safety statistics can be accurately reported. NNT/NNH cannot be calculated. Adverse event data are not reported in the available text. All numerical findings are not reported from the available abstract.
Practice implications
This was an explicitly designated exploratory pilot trial with a sample size of 40 children, which is appropriately powered for feasibility and signal detection but substantially underpowered to yield definitive efficacy conclusions. Because only the abstract is available — and that abstract is truncated before results are disclosed — no clinical interpretation of outcomes can be made without risk of fabrication. What can be said from the design: (1) The study population is narrowly defined (ages 5–12, dual diagnosis of asthma and AR, monosensitized or co-sensitized to house dust mite Dermatophagoides pteronyssinus), limiting generalizability to polysensitized children, adolescents, or those with non-mite sensitization patterns. (2) The intervention is mechanistically plausible — butyrate and heat-inactivated LGG have preclinical evidence supporting gut epithelial barrier reinforcement and regulatory T-cell modulation; DHA and quercetin have anti-type-2 inflammatory properties — but clinical translation in this population remains unestablished. (3) Exploratory pilot trials by definition should not change clinical practice; their purpose is to inform design parameters (effect size estimates, dropout rates, outcome feasibility) for adequately powered confirmatory trials. (4) The multicenter double-blind placebo-controlled design is methodologically appropriate for the exploratory phase. Clinicians should not incorporate this supplement regimen into standard asthma or allergic rhinitis management pending full publication of results and, ideally, replication in a larger definitive RCT. This summary is based solely on the available truncated abstract; the full results, secondary outcomes, biomarker data, and safety profile are not reported herein. __LIMITATIONS__ 1. Very small sample size (n=40): substantially underpowered for definitive efficacy conclusions; appropriately labeled as exploratory/pilot. 2. Abstract truncated: primary outcome results, secondary endpoints (likely including FeNO, serum IgE, eosinophil counts, cytokine profiles), and safety data are not available for review. 3. Restricted population: monosensitization to a single perennial allergen (D. pteronyssinus) limits generalizability to children with polysensitization or seasonal allergen profiles. 4. Age range 5–12 years only: findings may not apply to toddlers or adolescents. 5. Multicomponent intervention: attribution of any observed effect to a specific active ingredient is not possible; this is a combination product. 6. Surrogate and patient-reported outcomes (c-ACT, CARATkids, TNSS) used as co-primary endpoints; long-term clinical outcomes (exacerbation rates, lung function trajectory, prevention of asthma progression) not addressed in a 6-month pilot. 7. Funding source not reported: potential for undisclosed conflicts of interest cannot be assessed. 8. Blinding adequacy and allocation concealment details not described in the available excerpt. 9. Multicenter setting without reported site-level heterogeneity control. 10. Six-month follow-up insufficient to assess durability of any immunomodulatory effect or long-term safety. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ The INAPRA study is an appropriately designed exploratory pilot RCT evaluating a multicomponent immunonutritional supplement with postbiotic, prebiotic, omega-3, and phytochemical components in 40 children with comorbid allergic asthma and house dust mite–sensitized allergic rhinitis; however, the abstract is truncated and no quantitative results are available for appraisal. This trial should be understood strictly as a signal-generating, feasibility-informing study — its findings, when fully published, should be used to design an adequately powered confirmatory RCT before any clinical recommendation can be made. No change in current evidence-based management of pediatric allergic asthma or rhinitis is warranted on the basis of this study alone.