Research ArticleOriginal Research

Recommending Oral Probiotics to Reduce Winter Antibiotic Prescriptions in People With Asthma: A Pragmatic Randomized Controlled Trial

Timothy D. H. Smith, Hilary Watt, Laura Gunn, Josip Car and Robert J. Boyle
The Annals of Family Medicine September 2016, 14 (5) 422-430; DOI: https://doi.org/10.1370/afm.1970

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    CONSORT flow diagram showing participant recruitment and flow through the study.

    CONSORT = Consolidated Standards of Reporting Trials; PP = per protocol; ITT = intention to treat.

    aPP1 is 1 or more sets of probiotics ordered; PP2 is 2 or more sets of probiotics ordered. Each set included sufficient probiotics for 2 months.

  • Figure 2
    Figure 2

    Summarized effect size for the study primary outcome.

    ITT = intention to treat; OR = odds ratio; PP = per protocol.

    Note: Data represent the OR (95% CI) for 1 or more antibiotic prescriptions during the 6-month intervention period compared with control group. OR is unadjusted for the ITT analysis, and adjusted for age-group, sex, asthma severity, and use of any antibiotics in the 12 months before the study for per protocol analyses.

    aPP1 is 1 or more sets of probiotics ordered; PP2 is 2 or more sets of probiotics ordered. Each set included sufficient probiotics for 2 months.

Tables

  • Table 1

    Baseline Characteristics of Study Participants

    CharacteristicRandomized Control Group (n = 650)Randomized Intervention Group (n = 652)Obtaining any Probiotic Package (n = 123)Obtaining 2–3 Probiotic Packages (n = 88)
    Age-group, y
     5–18, No. (%)80 (12)80 (12)10 (8)7 (8)
     19–34, No. (%)95 (15)101 (15)7 (6)2 (2)
     35–59, No. (%)254 (39)251 (38)34 (28)21 (24)
     ≥60, No. (%)221 (34)220 (34)72 (59)58 (66)
    Age, median (range),a y48 (32–66)49 (32–65)64 (46–70)b65 (54–74)b
    Male, No, (%)277 (43)316 (49)c52 (42)42 (48)
    Body mass index, median (range)a26.8 (23.5–30.7)27.2 (24.2–30.7)28.2 (25.0–31.2)27.4 (24.9–30.9)
    Age when asthma diagnosed, median (range),a y31 (11–52)33 (11–50)46 (30–59)b47 (31–61)b
    Ethnic group
     White, No. (%)577 (89)595 (91)109 (89)82 (93)
     Black, No. (%)2 (0.3)1 (0.2)0 (0)0 (0)
     Asian, No. (%)4 (0.6)1 (0.2)0 (0)0 (0)
     Mixed, No. (%)45 (7)39 (6)12 (10)6 (7)
     Not specified, No. (%)22 (3)16 (3)2 (2)0 (0)
    Smoking status
     Never smoked, No. (%)385 (60)368 (57)76 (62)54 (61)
     Ex-smoker, No. (%)188 (29)200 (31)37 (30)29 (33)
     Current smoker, No. (%)66 (10)67 (10)7 (6)3 (3)
     Not specified, No. (%)11 (2)17 (3)3 (2)2 (2)
    Asthma severity
     Step 1, No. (%)103 (16)116 (18)15 (12)7 (8)
     Step 2 or 3, No. (%)283 (44)272 (42)51 (42)41 (47)
     Step 3 or 4, No. (%)202 (31)207 (32)40 (33)27 (31)
     Step 5, No. (%)62 (9)57 (9)16 (13)13 (15)
    Other disease registers
     Diabetes mellitus, No. (%)56 (9)37 (6)c5 (4)4 (5)
     Coronary heart disease, No. (%)36 (6)32 (5)10 (8)9 (10)
     Stroke or TIA, No. (%)11 (2)17 (3)2 (2)1 (1)
     COPD, No. (%)43 (7)46 (7)9 (7)8 (9)
     Cancer, No. (%)31 (5)37 (6)13 (11)c9 (10)c
     Rheumatoid arthritis, No. (%)5 (0.8)4 (0.6)1 (0.8)1 (1)
    In last 12 mo
     Any antibiotics, No. (%)330 (51)327 (50)71 (58)55 (63)c
     Oral corticosteroids, No. (%)132 (20)123 (19)26 (21)21 (24)
     Asthma review, No. (%)377 (58)373 (57)86 (70)c64 (73)d
     Influenza vaccine, No. (%)416 (64)409 (63)98 (80)b72 (82)b

    • COPD = chronic obstructive pulmonary disease; TIA = transient ischemic attack.

    • Note: Comparisons are made between randomized groups and for those within the intervention group who obtained probiotic packages at least once, and 2 to 3 times.

    • ↵a Range of 25th to 75th percentile.

    • ↵b P <.001.

    • ↵c P <.05

    • ↵d P <.01 comparing intervention group or per protocol groups obtaining probiotics with the control group (unadjusted analysis). No other such comparisons were significant.

  • Table 2

    Effects of Advice to Take Probiotics on Antibiotic Prescribing Outcomes

    OutcomeRandomized Control Group (n = 632)
    No. (%)    		Randomized Intervention Groupa (n = 638)
    No. (%)    		Obtaining Any Probiotic Packageb (n = 121)
    No. (%)    		Obtaining 2–3 Probiotic Packagesb (n = 86)
    No. (%)    		Randomized Intervention Groupa
    OR (95% CI)c    		Obtaining Any Probiotic Packageb
    AOR (95% CI)c    		Obtaining 2–3 Probiotic Packagesb
    AOR (95% CI)c
    Taken any selected antibiotic170 (26.9)177 (27.7)38 (31.4)28 (32.6)1.04 (0.82 to 1.34)1.08 (0.69 to 1.69)1.04 (0.62 to 1.75)
    Taken any antibiotic212 (33.5)216 (33.9)46 (38)32 (37.2)1.01 (0.80 to 1.28)1.09 (0.71 to 1.68)0.97 (0.58 to 1.6)
    Had URTI without wheeze, treated by antibiotics27 (4.3)30 (4.7)5 (4.1)4 (4.7)1.11 (0.65 to 1.88)1.15 (0.42 to 3.12)1.54 (0.5 to 4.72)
    Had respiratory episode, treated by antibiotics129 (20.4)143 (22.4)31 (25.6)24 (27.9)1.13 (0.86 to 1.47)1.16 (0.72 to 1.87)1.2 0.7 to 2.06)
    Mean No. (%)dMean No. (%)dMean No. (%)dMean No. (%)dIRR (95% CI)cIRR (95% CI)cIRR (95% CI)c
    Selected antibiotic course0.42 (17.4, 9.5)0.47 (16.3, 11.4)0.50 (9.8, 11.6)0.51 (19.8, 12.8)1.11 (0.88 to 1.38)1.02 (0.71 to 1.46)0.97 (0.64 to 0.46)
    Any antibiotic course0.59 (19.6, 13.9)0.61 (19.0, 14.9)0.64 (24.0, 14.0)0.63 (20.9, 16.3)1.03 (0.84 to 1.26)0.95 (0.69 to 1.32)0.88 (0.6 to 1.29)
    URTI without wheeze given antibiotic course0.04 (4.1, 0.2)0.05 (4.1, 0.6)0.04 (4.1, 0.0)0.05 (4.7, 0.0)1.24 (0.72 to 2.12)1.08 (0.41 to 2.83)1.36 (0.47 to 3.99)
    Combined all respiratory episodes given antibiotic course0.23 (18.2, 2.2)0.30 (16.1, 6.3)e0.32 (19.0, 6.6)0.35 (20.9, 7.0)1.31 (1.03 to 1.66)1.24 (0.87 to 1.78)1.26 (0.84 to 1.88)
    Mean £ (SD)Mean £ (SD)Mean £ (SD)Mean £ (SD)Diff, £ (95% CI)fDiff, £ (95% CI)fDiff, £ (95% CI)f
    Total cost per person of selected antibiotic1.49 (10.9)1.75 (16.58)4.41 (37.18)5.74 (44.08)0.25 (−1.29 to 1.79)2.33 (−3.80 to 8.46)3.50 (−5.26 to 12.27)
    Total cost per person of all antibiotics2.41 (11.68)2.38 (16.96)4.74 (37.18)5.98 (44.07)−0.04 (−1.62 to 1.54)1.74 (−3.84 to 8.51)2.81 (−5.14 to 12.15)

    • AOR = adjusted odds ratio; Diff = difference; IRR = incidence rate ratio; URTI = upper respiratory tract infection.

    • Note: Comparison is made between randomized groups comparing the intervention group with the control group, and the randomized control group with the per protocol groups after additional advice and obtaining probiotic.

    • ↵a From unadjusted analyses.

    • ↵b From analyses adjusted for age-group, sex, asthma severity and use of any antibiotics in 12 months before study.

    • ↵c Compared with the randomized control group.

    • ↵d Percentages with 1, with 2 or more.

    • ↵e P <.05 compared with the control group.

    • ↵f Compared with the randomized control group with boot-strapped confidence interval.

  • Table 3

    Effects of Advice to Take Probiotics on Respiratory Outcomes Not Related to Antibiotic Prescriptions

    OutcomeRandomized Control Group (n = 632)
    No. (%)    		Randomized Intervention Groupa (n = 638)
    No. (%)    		Obtaining Any Probiotic Packageb (n = 121)
    No. (%)    		Obtaining 2–3 Probiotic Packagesb (n = 86)
    No. (%)    		Randomized Intervention Groupa
    OR (95% CI)c    		Obtaining Any Probiotic Packageb
    AOR (95% CI)c    		Obtaining 2–3 Probiotic Packagesb
    AOR (95% CI)c
    Had any URTI without wheeze43 (6.8)48 (7.5)11 (9.1)7 (8.1)1.11 (0.73–1.71)1.56 (0.76–3.20)1.5 (0.63–3.59)
    Had any LRTI without wheeze63 (10.0)87d (13.6)17 (14.0)11 (12.8)1.43 (1.01,2.01)1.29 (0.71–2.33)1.07 (0.53–2.18)
    Had any asthma exacerbations, wheeze85 (13.4)84 (13.2)19 (15.7)15 (17.4)0.98 (0.71–1.35)1.12 (0.64–1.99)1.17 (0.61–2.23)
    Had any respiratory infection177 (28.0)188 (29.5)40 (33.1)29 (33.7)1.07 (0.84–1.37)1.19 (0.77–1.84)1.16 (0.70–1.93)
    Received influenza vaccine during trial430 (68.0)454 (71.2)111 (91.7)e78 (90.7)f1.16 (0.91–1.47)4.34 (2.12–8.91)2.95 (1.31–6.65)
    Received asthma review during trial221 (35.0)207 (32.4)47 (38.8)36 (41.9)0.89 (0.71–1.13)0.94 (0.62–1.43)1.01 (0.62–1.63)
    Mean No. (%)gMean No. (%)gMean No. (%)gMean No. (%)gIRR (95% CI)cIRR (95% CI)cIRR (95% CI)c
    URTIs without wheeze0.08 (5.4, 1.4)0.09 (6.6, 0.9)0.09 (9.1, 0.0)0.08 (8.1, 0.0)1.03 (0.67–1.58)1.15 (0.55–2.42)1.06 (0.43–2.62)
    LRTIs without wheeze0.12 (8.5, 1.4)0.1(10.8, 2.8)d0.17 (10.7, 3.3)0.15 (10.5, 2.3)1.47 (1.05–2.04)1.34 (0.78–2.32)1.12 (0.58–2.16)
    Asthma exacerbations or wheeze0.17 (11.1, 2.4)0.16 (10.5, 2.7)0.18 (13.2, 2.5)0.21 (14.0, 3.5)0.95 (0.70–1.31)1.00 (0.59–1.68)1.03 (0.58–1.84)
    Total respiratory episodes0.37 (21.4, 6.6)0.42 (20.5, 8.9)0.45 (24.0, 9.1)0.44 (24.4, 9.3)1.13 (0.92–1.38)1.17 (0.84–1.62)1.09 (0.75–1.59)

    • AOR =adjusted odds ratio; IRR = incidence rate ratio; LRTI = lower respiratory tract infection; URTI = upper respiratory tract infection.

    • Note: Comparison is made between randomized groups comparing the intervention group with the control group and between the per protocol groups of participants after additionaladvice and obtaining probiotics during the study, to the randomized control group.

    • ↵a From unadjusted analyses.

    • ↵b From analyses adjusted for age-group, sex, asthma, severity, any use of any antibiotics in 12 months before the study.

    • ↵c Compared with the randomized control group.

    • ↵d P <.05 compared with the randomized control group.

    • ↵e P <.001 compared with the control group.

    • ↵f P <.01 compared with the control group.

    • ↵g Percentages with 1, with 2, or more.

  • Table 4

    Serious Adverse Events

    Event CategoryRandomized Control Group (n = 632)Randomized Intervention Group (n = 640)Obtaining Any Probiotic Package (n = 122)Obtaining 2–3 Probiotic Packages (n = 87)
    No.% (95% CI)No.% (95% CI)No.% (95% CI)No.% (95% CI)
    Respiratory101.6 (0.8–2.9)60.9 (0.3–2.0)10.8 (0.02–4.5)11.1 (0.03–6.2)
    Gastrointestinal60.9 (0.3–2.1)101.6 (0.8–2.9)00.0 (0.0–3.0)00 (0–4.2)
    Infection (excluding above)20.3 (0.04–1.1)40.6 (0.2–1.6)21.6 (0.2–5.8)11.1 (0.03–6.2)
    Other203.2 (1.9–4.8)314.8 (3.3–6.8)10a8.2 (4.0–14.6)66.9 (2.6–14.4)

    • Note: Each category of event is compared according to the randomized groups and the per protocol groups of those receiving additional advice who obtained probiotics, counting number of participants affected by each category of event.

    • ↵a P <.05 compared with control group, adjusted for age and sex.

Additional Files

  • The Article in Brief

    Recommending Oral Probiotics to Reduce Winter Antibiotic Prescriptions in People With Asthma: A Pragmatic Randomized Controlled Trial

    Timothy D. H. Smith , and colleagues

    Background Previous studies have shown that orally administered probiotics may prevent respiratory tract infections and associated antibiotic use.

    What This Study Found The study finds no evidence to support earlier findings that probiotics may prevent respiratory tract infections. In a randomized trial of 1,302 asthmatic patients aged five years and older, researchers assessed whether advice to take probiotic treatment implemented as part of routine winter infection advice could reduce antibiotic prescription rates and respiratory tract infections. Participants in the intervention group received a leaflet that recommended taking a probiotic capsule daily, as well as free access to the supplements. Although uptake of probiotics was low--only 20 percent of patients in the intervention group accessed the recommended probiotics--outcomes were similar between the two groups.

    Implications

    • The authors conclude that real-world use of probiotics to prevent winter infections and reduce antibiotic use cannot yet be recommended despite earlier positive findings--at least not in older children and adults with asthma.

  • Supplemental Appendixes

    Supplemental Appendixes

    Files in this Data Supplement:
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Get Permissions

Jump to section

Subjects

Keywords