Does Lactoplantibacillus plantarum DR7 Reduce Days of Upper Respiratory Tract Infections and Fever? A Post‐Hoc Analysis of a Randomized, Placebo‐Controlled Trial

Abstract

Objectives and Hypothesis Upper respiratory tract infections (URTIs) are amongst most common causes of doctor visits, days of work leave and school leave. Lactoplantibacillus plantarum DR7 (KCTC 13909BP) is a probiotic strain previously shown to modulate the tryptophan-serotonin-kynurenine pathway in human hosts. Previous results indicated a positive effect of a 3-month intervention with L. plantarum DR7 (109cfu/day) on individual nasal, pharyngeal and flu-like symptoms in a randomized, double-blinded trial against placebo in 109 adult subjects. We hypothesized that this probiotic could achieve a significant reduction of patient-days of URTI and fever. Also, we wanted to assess whether clinical or demographic traits may influence this effect. Methods Study outcomes were total patient-days of URTI and patient-days of fever during the 3-month intervention. Patient-days of URTI were estimated from symptoms questionnaire using two alternative definitions: i) duration of the longest-lasting symptom, and ii) average duration of symptoms. Patient-days of fever were taken directly from the questionnaire. Pairwise correlations between study outcomes and clinical and demographic parameters (age, sex, body mass index, smoker status, urban vs rural living, income above or below national average, and URTI episodes in the 4 weeks prior to study enrolment) were assessed by Spearman test. Differences in patient-days between groups were assessed by Chi-square (unadjusted) or Mantel-Haenszel tests (adjusted). Significance thresholds were multiplicity-corrected by Bonferroni-Holm method. All procedures on study subjects had been approved by the Internal Review Board of Universiti Sains Malaysia and adhered to the Helsinki Declaration. Summary of Results Of all clinical and demographic parameters analyzed, only recent URTI significantly correlated to study outcomes once corrected for multiplicity (rho=0.27-0.30, all p≤0.005). Compared to subjects without recent URTI (n=71), those with recent URTI (n=38) had increased patient-days of URTI (both definitions) and patient-days of fever (all p<0.001). History of recent URTI was numerically higher in probiotic than placebo group (43% vs 27%, Chi-square p=0.078). Probiotic intervention (n=56) resulted in significantly fewer patient-days of URTI compared to placebo (n=53) according to both definitions, as well as fewer patient-days of fever (all p<0.05 unadjusted, p<0.001 adjusted for recent URTI history; see Table 1). Conclusion Compared to placebo, intervention with L. plantarum DR7 significantly reduced patient-days with URTI by 20%, and patient-days with fever by 27%. Patient history of recent URTI significantly increased the risk of URTI during the intervention, and significance of probiotic efficacy was improved upon accounting for said parameter.