Wang 2015.
| Methods | Four‐arm parallel‐group double‐blind randomised placebo‐controlled trial conducted from December 2011 until September 2013 | |
| Participants | 220 children and adolescents from 1 to 18 years of age with moderate to severe atopic dermatitis (SCORAD > 15) diagnosed according to the criteria of Hanifin and Rajka with symptoms present for at least 6 months before the study and with atopy as shown by at least 1 positive skin test (weal size ≧ 3 mm) or 1 positive RAST (IgE ≥ 0.7 kU/L) test to any common food or environmental allergens. Randomisation was done at a 1:1 ratio: 55 participants were randomised in each arm Excluded were patients on systemic corticosteroids, immunosuppressive therapy, or antibiotic or antimycotic treatment 4 weeks before the study, or using antihistamine 3 days before enrolment; and those who used probiotic preparations within 4 weeks before the study. Also excluded were patients with immune deficiency or other major medical problems Setting: secondary paediatric centre Country: Taiwan |
|
| Interventions | Four intervention arms: first arm received Lactobacillus paracasei GMNL‐133 (LP) at a dose of 2 × 10⁹ CFUs/d. Second arm received Lactobacillus fermentum GM‐090 (LF) at a dose of 2 × 10⁹ CFUs/d. Third arm received Lactobacillus paracasei GMNL‐133 (LP) and Lactobacillus fermentum GM‐090 (LF) at a dose of 4 × 10⁹ CFUs/d. Fourth arm received placebo. Interventions were given orally in capsule form for 3 months During the study, corticosteroids, antibiotics, calcineurin inhibitors, antihistamines, and other probiotics were not permitted, with the exception of topical corticosteroids (fluticasone propionate) in case of severe flares and itching. All patients applied emollients and were educated on skin care |
|
| Outcomes | For AD: SCORAD, Children's Dermatology Life Quality Index (CDLQI) and Family Dermatology Life Quality Index (FDLQI) at baseline and at 1, 2, 3, and 4 months Changes in total serum IgE and skin prick test reactivity, serum and urine biomarkers, and faecal probiotic species composition at baseline and at 3 months For asthma: GINA guideline asthma severity |
|
| Notes | Trial registration: NCT01635738. Approval by the Ethics Committee of the Taipei Hospital Ministry of Health and Welfare GenMont Biotec Inc.: probiotic manufacturer that provided study costs for probiotics. No information on conflicts of interest |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Participants were randomised, using computer‐generated 4‐block design lists, drawn up by a statistician, with stratification according to age, gender, AD severity, and current use of topical steroids" |
| Allocation concealment (selection bias) | Low risk | Comment: probably done and judged as having low risk of bias |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Patients were enrolled by the investigator and sequentially assigned a patient number connected to a code. Capsules were prepared and coded by GenMont Biotec Inc, with cGMP facilities and dispensed by the study nurse" ‐ "All investigators, study nurses and participants were blind to treatment assignment for the duration of the study" Judgement: probably done |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "Patients were enrolled by the investigator and sequentially assigned a patient number connected to a code. Capsules were prepared and coded by GenMont Biotec Inc, with cGMP facilities and dispensed by the study nurse" ‐ "All investigators, study nurses and participants were blind to treatment assignment for the duration of the study" Judgement: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quotes: "Finally analysed 100% of LP, 96% of LF, 98% of LP + LF group, and 96% of placebo" ‐ "Intention‐to‐treat analysis regardless of compliance" Judgement: low risk of attrition bias |
| Selective reporting (reporting bias) | Low risk | All outcomes reported |
| Other bias | Unclear risk | GenMont Biotec Inc.: probiotic manufacturer that provided study costs for probiotics. It is not clear what the role of the sponsor was in data analysis and publication; hence the study was judged to be at unclear risk of bias |