Prevention of Asthma and Allergy by Probiotic Lactobacillus GG
Condition: Allergic Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      Given that asthma results from a complex interaction between genetic susceptibility and
      environmental factors and rates of childhood asthma are increasing, primary prevention has to
      focus on modifiable aspects such as nutrition. There a implications from epidemiology that
      food supplementation with probiotics given to atopic mothers in pregnancy and during
      lactation can prevent the development allergies in the offspring. Children with atopic
      dermatitis are at increased risk (up to 80%) of developing persistent respiratory tract
      disease. Our trial examined whether probiotics are able to prevent allergic sensitization and
      allergic asthma when given to 6-24 month old infants at an increased risk of allergies.
    

Detailed description: 
      In our investigator-initiated prospective study, a total of 170 children with at least two
      episodes of wheezing and a first degree family history of atopic disease were recruited from
      our walk-in clinic between October 2002 and October 2004. We chose this relatively long
      period of time to exclude a seasonal selection bias (e.g., upper airway infections or
      airborne allergens). 131 eligible children (6 to 24 month old) were randomly assigned to a
      double-blind dietary supplementation with Lactobacillus rhamnosus strain GG ATCC 53103 (LGG)
      twice daily or placebo over six months. A computerized randomization schedule was prepared by
      a biostatistician with allocation and dispensing of capsules by the distributor of LGG. The
      capsules were matched for size, shape, and volume of content, which was reconstituted with 5
      ml water and then given by spoon. Compliance was monitored by use of a capsule chart
      (completed by parents) and capsule counts. The parents were asked to keep a diary provided by
      the study group. Clinical monitoring was done for one year: before the intervention (visit
      1), after 3, 6, 9, and 12 months (visit 2 to 5). It encompassed episodes of asthmatic
      exacerbations defined as cough and wheeze, numbers and days of associated hospitalizations,
      symptom free days, days without use of rescue medication (steroid suppositoria, a frequently
      used device in Western Europe), and associated inhalative steroid and beta-agonist use.
      Children underwent a physical examination including determination of the severity scoring of
      atopic dermatitis (SCORAD) index to assess eczema severity examination on each study visit to
      our walk-in clinic. To ensure consistency, the same investigator performed all SCORAD
      assessments. Atopic eczema was confirmed by characteristical cutaneous findings, pruritus,
      and chronic relapsing course. This last criterion was fulfilled if the child presented eczema
      for at least one month on at least one visit. Asthma diagnosis was based on an algorithm from
      an international paediatric asthma consensus group. Asthma was diagnosed if the child had
      chronic or recurrent cough, wheeze or shortness of breath, or both, and if other diagnosis
      were excluded and trial antiasthmatic treatment was effective. Blood samples were taken on
      visit 1, 3, and 5. Sensitization to common dietary and respiratory allergen was measured by
      total and antigen specific IgE assays against hen's egg, cat epithelia, house dust mite
      (D1+2), birch pollen, milk protein, lactalbumin, timothy pollen, horse epithelia and
      alternaria by chemiluminescence-immunoassay. This highly-sensitive assay is suitable
      especially for the determination of low value of specific IgE. Additionally, eosinophilic
      cationic protein and eosinophils were determined.

      Primary outcome measures were the asthma-related clinical events. Secondary measures were the
      serum concentrations of IgE, specific IgE, ECP, Eos, IL-2 soluble receptor alpha (IL-2Rα, to
      reflect T-cell related inflammatory state) and transforming growth factor beta (TGFβ, a
      profibrotic factor whose expression is increased in asthmatics, indicating airway remodeling.
      All parents supplied written informed consent prior to the study. Human experimentation
      guidelines of Good Clinical Practice, the German Drug Act and the declaration of Helsinki /
      Hong Kong were followed in the conduct of clinical research.
    

Intervention name(s): Lactobacillus rhamnosus strain GG ATCC 53103 (LGG, 1010 cfu)
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Prevention
Keywords: probiotics; LGG; praevention; allergic asthma; children