Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC
Leyer and colleagues conducted a randomized trial with 2 treatment arms and 1 control arm, in a preschool setting in China.
The subjects took the tested probiotics (or placebo) twice a day over a 6-month period during the 2005-2006 winter season. The children were randomized 1-1-1 to the 3 groups, with 1 treatment group receiving Lactobacillus acidophilus (single-agent) in a powder and the second treatment group receiving a combination of Lactobacillus acidophilus and Bifidobacterium animalis (combination), also as a powder. The control group received a powder placebo that was indistinguishable from the treatment granules.
All participants took their powders twice a day with milk. Weekday administrations were conducted by preschool personnel, and families administered the compounds on weekends.
The authors hypothesized that either treatment group would prove superior to placebo in reducing both incidence and duration of respiratory illnesses in the subjects, but they also hypothesized that the children in the combination treatment group would fare better than the single-agent group.
Episodes of illness were recorded by either the preschool staff (weekdays) or parents (weekends) in symptom diaries. Any symptom experienced in a day was considered as having been experienced for 24 hours for the sake of analyses. The authors also evaluated absenteeism from school via school record review.
Three hundred twenty-six children were randomized, with 104-112 subjects per group having complete data at the end of the study. Each group lost approximately 25-27 subjects, with no clear differences for why the children withdrew among the groups. When looking at school attendance, 28% of all children were absent at least 1 day during the study period, but this rate was much higher among placebo children (49%) compared to either treatment group (18% each).
The single-agent group had lower rates of fever, cough, and use of antibiotics compared to placebo, while the combination treatment group had lower rates of fever, cough, rhinorrhea, and antibiotic use compared to placebo. For almost all symptoms, the combination group had point estimates (rates) that were lower than those of the single-agent group (eg, 6-month incidence rate of "fever" was 64% in placebo, 28% in single-agent treated, and 16% in combination agent treated subjects), but the differences between the two treatment groups did not reach statistical significance except when the symptoms were all grouped into "any symptom." In a similar pattern, the total symptom duration was longer for placebo children compared to either treatment group. There were insufficient numbers of children with diarrhea to complete comparisons between the groups.
The authors conclude that use of probiotics reduced the incidence and duration of upper respiratory symptoms and antibiotic use. The authors also suggest that there appeared to be a trend toward a greater effect among participants in the combined treatment group compared to the single-agent treatment group.
These data are interesting for the magnitude of potential benefit they show. Reducing preschool absentee rates by > 50% is remarkable, and the savings of that alone for working families would likely make this intervention worthwhile financially. I am concerned about why the authors were unable to evaluate effects on diarrhea in a preschool setting. They report that 24 subjects had diarrhea, but they do not present the analyses. It is also difficult to know how American and Chinese preschool environments differ and if probiotic use would provide similar benefits in the United States. While the results are intriguing, it would be helpful to see the study replicated before making any recommendations regarding routine use of probiotics in older children to prevent upper respiratory infections and symptoms.