Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy.

2016-07-01
Allergy and asthma proceedings 37(4)
- Joanna Jerzynska
- Wlodzimierz Stelmach
- Joanna Balcerak
- Katarzyna Woicka-Kolejwa
- Blazej Rychlik
- Andrzej Blauz
- Marcin Wachulec
- Piotr Stelmach
- Pawel Majak
- Iwona Stelmach

PubMed: 27401319
DOI: 10.2500/aap.2016.37.3958

Study Design

Type: Randomized Controlled Trial (RCT)
Population: One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis
Methods: 5-month prospective, randomized, double-blind, placebo-controlled trial; 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo
Blinding: Double-blind
Duration: 5 months

Background

An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy.

Objective

To compare the clinical and immunologic efficacy of SLIT given alone and, to enhance clinical efficacy, given with probiotic or vitamin D supplementation.

Methods

One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo. The control group included children with allergy who did not qualify for immunotherapy. Primary end points included a symptom-medication score, lung function, and exhaled nitric oxide concentration. The secondary end point was the immunologic efficacy measured by the following: CD4(+)CD25(+)Foxp3(+) (forkhead box P3) cells, Toll-like receptor (TLR) 4, interleukin (IL) 1, IL-6, tumor necrosis factor, IL-10, and transforming growth factor β-1 levels in cell culture supernatants.

Results

Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group. In the SLIT-probiotic group, between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1). An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor β-1 production were independently associated with a better clinical effect of SLIT in children.

Conclusions

We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT. Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis.

Research Insights

Lactobacillus rhamnosus GG→Improved Lung Function
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Lactobacillus rhamnosus GG→Increased Regulatory T Cell Count
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Lactobacillus rhamnosus GG→Increased Transforming Growth Factor-β Levels
An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor β-1 production were independently associated with a better clinical effect of SLIT in children.
Effect
Neutral
Effect size
Small
Dose
1000 IU/day
Lactobacillus rhamnosus GG→Reduced Symptom-Medication Score
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Lactobacillus rhamnosus GG→Reduced Toll-Like Receptor 4 Positive Cell Count
higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1).
Effect
Neutral
Effect size
Small
Dose
1000 IU/day
Vitamin D→Improved Lung Function
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Vitamin D→Increased Regulatory T Cell Count
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Vitamin D→Increased Transforming Growth Factor-β Levels
An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor β-1 production were independently associated with a better clinical effect of SLIT in children.
Effect
Neutral
Effect size
Small
Dose
1000 IU/day
Vitamin D→Reduced Symptom-Medication Score
Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group.
Effect
Beneficial
Effect size
Moderate
Dose
1000 IU/day
Vitamin D→Reduced Toll-Like Receptor 4 Positive Cell Count
higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1).
Effect
Neutral
Effect size
Small
Dose
1000 IU/day