. 2020 Jan 22;2020(1):CD012949. doi: 10.1002/14651858.CD012949.pub2

Comparison 1. Probiotic versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Pulmonary exacerbation (mean number per participant)	4	225	Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.68, 0.03]
1.1 Over 3 months and up to 6 months	3	148	Mean Difference (IV, Random, 95% CI)	‐0.39 [‐0.80, 0.02]
1.2 Over 9 months and up to 12 months	1	77	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.75, 0.95]
2 Pulmonary exacerbation (duration of antibiotic therapy ‐ any route)	2	127	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐9.04, 8.14]
2.1 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	‐2.0 [‐12.89, 8.89]
2.2 Over 9 months and up to 12 months	1	77	Mean Difference (IV, Random, 95% CI)	2.10 [‐11.88, 16.08]
3 Faecal calprotectin (µg/g)	4	177	Mean Difference (IV, Random, 95% CI)	‐47.41 [‐93.28, ‐1.54]
3.1 Up to 3 months	2	69	Mean Difference (IV, Random, 95% CI)	‐105.02 [‐205.23, ‐4.81]
3.2 Over 3 months and up to 6 months	2	108	Mean Difference (IV, Random, 95% CI)	‐32.14 [‐83.73, 19.45]
4 Faecal calprotectin (µg/g) ‐ change from baseline ‐ sensitivity analysis	3	130	Mean Difference (IV, Random, 95% CI)	‐31.17 [‐81.56, 19.22]
4.1 Up to 3 months	1	22	Mean Difference (IV, Random, 95% CI)	‐11.0 [‐246.06, 224.06]
4.2 Over 3 months and up to 6 months	2	108	Mean Difference (IV, Random, 95% CI)	‐32.14 [‐83.73, 19.45]
5 Faecal calprotectin (µg/g) ‐ post treatment ‐ sensitivity analysis	3	119	Mean Difference (IV, Random, 95% CI)	‐45.46 [‐176.25, 85.32]
5.1 Up to 3 months	2	69	Mean Difference (IV, Random, 95% CI)	‐107.29 [‐171.20, ‐43.38]
5.2 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	77.0 [3.11, 150.89]
6 Serum cytokines	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
6.1 TNF‐α (pg/ml)	2	89	Mean Difference (IV, Random, 95% CI)	0.20 [‐0.72, 1.13]
6.2 IL‐8 (pg/ml)	2	95	Mean Difference (IV, Random, 95% CI)	26.93 [‐46.25, 100.11]
6.3 IL‐1β (pg/ml)	1	41	Mean Difference (IV, Random, 95% CI)	0.30 [‐0.28, 0.88]
6.4 IL‐6 (pg/ml)	1	41	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.68, 0.10]
6.5 IL‐10 (pg/ml)	1	41	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.43, 0.33]
6.6 NOx (μmol/L)	1	41	Mean Difference (IV, Random, 95% CI)	0.08 [‐0.26, 0.42]
6.7 IL‐12 (pg/ml)	1	41	Mean Difference (IV, Random, 95% CI)	0.53 [0.10, 0.96]
6.8 MPO (mU/ml)	1	41	Mean Difference (IV, Random, 95% CI)	0.05 [‐0.14, 0.24]
7 Sputum cytokines ‐ change from baseline	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
7.1 TNF‐α (pg/ml)	1	48	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.94, 0.54]
7.2 IL‐8 (pg/ml)	1	54	Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.92, 0.52]
8 Adverse events	5		Risk Ratio (IV, Random, 95% CI)	Subtotals only
8.1 Mortality (all causes)	5	310	Risk Ratio (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Serious adverse reaction	5	310	Risk Ratio (IV, Random, 95% CI)	3.0 [0.13, 67.06]
8.3 Adverse reaction	5	310	Risk Ratio (IV, Random, 95% CI)	3.0 [0.49, 18.46]
9 Height (z score) ‐ post treatment	2	91	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.27, 0.47]
9.1 Up to 3 months	1	41	Mean Difference (IV, Random, 95% CI)	0.21 [‐0.62, 1.04]
9.2 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	0.07 [‐0.34, 0.48]
10 Weight (z score) ‐ post treatment	2	91	Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.51, 0.05]
10.1 Up to 3 months	1	41	Mean Difference (IV, Random, 95% CI)	‐0.4 [‐0.70, ‐0.10]
10.2 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.30, 0.08]
11 Weight (kg) ‐ change from baseline	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
11.1 Over 3 months and up to 6 months	1	38	Mean Difference (IV, Random, 95% CI)	1.2 [‐0.04, 2.44]
12 BMI (z score)	2	91	Mean Difference (IV, Random, 95% CI)	‐0.02 [‐0.25, 0.22]
12.1 Up to 3 months	1	41	Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.54, 0.32]
12.2 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.26, 0.31]
13 Lung function (FEV₁ % predicted)	5	284	Mean Difference (IV, Random, 95% CI)	1.36 [‐1.20, 3.91]
13.1 Up to 3 months	1	41	Mean Difference (IV, Random, 95% CI)	‐8.07 [‐19.87, 3.73]
13.2 Over 3 months and up to 6 months	3	166	Mean Difference (IV, Random, 95% CI)	2.22 [‐0.51, 4.94]
13.3 Over 9 months and up to 12 months	1	77	Mean Difference (IV, Random, 95% CI)	‐2.80 [‐12.13, 6.53]
14 Lung function (FEV₁ % predicted) ‐ change from baseline ‐ sensitivity analysis	3	166	Mean Difference (IV, Random, 95% CI)	2.22 [‐0.51, 4.94]
14.1 Over 3 months and up to 6 months	3	166	Mean Difference (IV, Random, 95% CI)	2.22 [‐0.51, 4.94]
15 Lung function (FEV₁ % predicted) ‐ post treatment ‐ sensitivity analysis	3	168	Mean Difference (IV, Random, 95% CI)	‐1.31 [‐7.10, 4.48]
15.1 Up to 3 months	1	41	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐14.48, 11.68]
15.2 Over 3 months and up to 6 months	1	50	Mean Difference (IV, Random, 95% CI)	0.10 [‐8.85, 9.05]
15.3 Over 9 months and up to 12 months	1	77	Mean Difference (IV, Random, 95% CI)	‐2.80 [‐12.13, 6.53]
16 Hospitalisations (number ‐ all causes)	2	115	Mean Difference (IV, Random, 95% CI)	‐0.44 [‐1.41, 0.54]
16.1 Over 3 months and up to 6 months	1	38	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐1.74, ‐0.26]
16.2 Over 9 months and up to 12 months	1	77	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.25, 0.25]
17 HRQoL (validated questionnaire)	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
17.1 PedsQL^TM 4.0 SF 15 ‐ Parent Report (performed 3 months post 1 month intervention period)	1	37	Std. Mean Difference (IV, Random, 95% CI)	0.87 [0.19, 1.55]
17.2 PedsQL^TM 4.0 SF 15 ‐ Child Report (performed 3 months post 1 month intervention period)	1	37	Std. Mean Difference (IV, Random, 95% CI)	0.59 [‐0.07, 1.26]