Reporting effectiveness of an extract of three traditional Cretan herbs on upper respiratory tract infection: results from a double-blind randomized controlled trial

Abstract

Ethnopharmacological relevance: Observations from the island of Crete, Greece suggest that infusions of traditional Cretan aromatic plants, well known for their ethnopharmacological use in Eastern Mediterranean region and Near East, could be effective in the prevention and treatment of upper respiratory tract infections, including viral-induced infections. The aim of this study was to report the effectiveness of an essential-oil extract of three Cretan aromatic plants in the treatment of cases with an upper respiratory tract infection.

Materials and methods: A double blind randomized controlled trial was implemented between October 2013 and February 2014. An essential-oil extract of Cretan aromatic plants in olive oil (total volume of 15ml of essential oil per litre of olive oil) was administered as 0.5ml soft gel capsules, twice a day, for 7 days. Placebo treatment was 0.5ml olive oil in soft gel capsules. Eligible patients were those presenting for clinical examination in the selected setting with signs and symptoms of upper respiratory tract infection that had begun within the previous 24 hours. Real-Time Polymerase Chain Reaction (PCR) was used for the detection of respiratory viruses. The primary outcome was the severity and duration of symptoms of upper respiratory tract infection, assessed using the Wisconsin Upper Respiratory System Survey (WURSS-21) questionnaire. A secondary outcome of interest was the change in C-reactive protein (CRP) status.

Results: One hundred and five patients completed the study: 51 in the placebo group, and 54 in the intervention (treated) group. Baseline characteristics were similar in the two groups. No statistically significant differences were found in symptom duration or severity between the two groups, although small and clinically favorable effects were observed. When the analysis was restricted to subjects with a laboratory-documented viral infection, the percentage of patients with cessation of symptoms after 6 days of treatment was 91% in the intervention group and 70% in the control group (p=0.089). At baseline, one third of the patients in each group had elevated CRP levels. At follow-up, the respective proportions were 0% in the intervention group and 15% in the placebo group (p=0.121). The data were also in a favorable direction when 50% and 80% symptom reduction points were considered for specific virus types.

Conclusions: Compared with placebo the essential-oil extract of three Cretan aromatic plants provided no detectable statistically significant benefit or harm in the patients with upper respiratory illness, although descriptive differences were identified in favorable direction mainly in the virus-positive population.

Keywords: 2.100: antiviral; 2.172: Clinical trials; 2.641: Traditional medicine Europe; Mediterranean; Near East.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Figures

Graphical abstract

Fig. 1

Flowchart of the study. Graphical representation of the RCT study design. See Material and methods and Results for further details.

Fig. 2

Frequency charts of detected virus strains. Distribution of viruses׳ strains in our study population. This shows the different viruses strains while abscissa shows the percentage of positive patients in the study. The black part of the column shows virus positive patients in the control, while the red part the virus positive patients in the intervention group. (For interpretation of the references to color in this figure legend,the reader is referred to the web version of this article.)

Fig. 3

Daily median WURRS-21 scores and 95% CIs per study groups. (A) Boxplots of Daily WURSS-21 scores per study group. (B) Boxplots of Daily WURSS-21 scores per study group in patients with symptoms (symptomatic patients). (C) Boxplots of Daily WURSS-21 scores per study group in virus positive patients.

Fig. 4

Daily probability of symptom cessation. Whisker plots of the daily probabilities for symptom cessation and 95% Confidence intervals (CI׳s) per group in the total population of the study. (A) All patients and(B) virus-positive patients.

Fig. 5

Evolution of the disease in selected virus-positive groups, according to the virus strain detected. Figure depicts the WURSS-21 (mean±SE) values of the daily WURSS score in: (A) human metapneumovirus (hMpv), (B) human rhinovirus (hRv), (C) human parainfluenza virus-NL63, and (D) the pandemic H1, Influenza A virus (H1N1). Table presented in (E) shows the time in days at which half (50%) and 80% of WURSS-21 encoded symptoms were relieved in the control and the intervention group, according to the virus found at day 1. Data were calculated through a logistic fit of curves presented in A–D.

Fig. 6

CRP normalization. Line-plot representing normalization of CRP values (from day 1 to day 7) in the total and the virus-positive population.