Echinacea for Preventing and Treating the Common Cold

• Abstract
• Introduction
• Evaluation of Recent Reviews
• Different Echinacea preparations used
• Different trial approaches and outcome measurements used
• Quality of Studies
• Conclusions
• References

Abstract

Echinacea preparations are widely used for common cold. Many consumers and healthcare professionals are not aware that products available under the term Echinacea may differ in their composition, due to the use of different species, plant parts, extraction methods and addition of other components. In 2005, a Cochrane review has been published to provide objective evidence whether the various Echinacea preparations are more effective than no treatment, more effective than placebo or similarly effective to other treatments in the prevention and the treatment of the common cold. In contrast to other reviews, the specific criteria for pooling of data from different trials have been predefined to assure a meaningful meta-analysis. In the meantime two further meta-analyses have been published. In the present mini-review, these latest meta-analyses are evaluated and discussed.

Introduction

Acute upper respiratory infection (URI), especially the common cold, is the second most common diagnosis in physician’s offices and the most common discharge diagnosis in emergency departments [1]. According to a Cochrane review, the evidence on the benefits of antibiotics in the treatment of URIs does not warrant their use [2], since most URIs are viral infections. Therefore, common cold is often treated with over-the-counter medicines, often involving phytotherapeutics. Echinacea is one of the most extensively used plants for the prevention and treatment of URIs and currently in the US market the second top-selling herbal product [3]. The products contain one or more species of Echinacea (E. angustifolia, E. purpurea and E. pallida), and may contain extracts of roots, or aerial parts, or both. These preparations contain quite a different profile of constituents with various amounts and hence are not therapeutically comparable [4].

Recently, several meta-analyses have been published which evaluated the available evidence from clinical trials in a rather different manner. The concept and the outcome of these reviews shall be discussed and recommendations shall be developed for future clinical studies with Echinacea.

Evaluation of Recent Reviews

In one meta-analysis, all performed clinical trials were pooled regardless of the product tested or the trial approach used [5], the second included only trials with experimentally induced infections [6] while the third used a lot of predefined criteria for pooling [7] ([Table 1]). The Cochrane meta-analysis identified the problems inherent in assessing the efficacy of Echinacea preparations using this pooling technique, namely lack of comparability of all available preparations, study designs and outcome measures used. Furthermore, a crucial factor in the investigation of a cold remedy is the timely initiation of treatment. In various clinical Echinacea studies, the start of medication varied from the time of occurrence of first symptoms to several hours afterwards, therefore it is not surprising that the outcomes differ considerably and result in a critical divergence [6], [8], [9]. Thus, the developed experimental induction system allows previously uncontrollable variables, such as time to initiation of treatment, virus type and dose, and immune competence of volunteers, to be standardized [9]. It provides a homogeneous study design and was found to be suitable for performing meta-analysis. If such criteria like, e. g., pooling of only experimentally induced studies, pooling the same control strategy (placebo, no treatment, treatment with another intervention), pooling trials with treatment given for the same purpose (prevention or treatment) or pooling trials using the same preparation and in similar dosage, were not predefined, as is the case in the recently published trial by Shah et al. [5], it is evident why a discrepancy of results emerges. Compared to the Cochrane review [7], the findings and conclusions in the Shah study [5] are much more positive. The most likely reason for that is that Shah et al. combined trials regardless of the product tested and included trials in which an Echinacea preparation is combined with another herbal product.

Different Echinacea preparations used

In previous studies, often the quality of the herb or even its species or dosage was not specified, thus making the findings not precise and not reproducible. In 16 randomised controlled trials summarised in the Cochrane database, only eight (50 %) reported the exact characterisation of the herbal remedy being used [7]. In the three experimental infection studies pooled by Schoop and colleagues only one (33 %) has been included without content details of the tested Echinacea product [6]. In the 14 randomised clinical trials included in the meta-analysis by Shah et al., five (36 %) reported the chemical profiling of the herbal product used [5]. That means the newly published meta-analysis pooled results for all Echinacea preparations although the original publication did not adequately describe the preparations tested. This lack of information needs to be taken into account when research on Echinacea is evaluated. Besides the lack of quality analysis, the great heterogeneity of preparations tested in clinical trials makes general statements and conclusions difficult. Most of the preparations used in those trials were pressed juices (stabilised with alcohol), alcoholic tinctures, or tablets made from dried extracts. That is why future clinical trials should take care of a proper characterisation of the products and should comply with the guidelines for reporting clinical trials of herbal medicine [10].

Different trial approaches and outcome measurements used

Three different study approaches: prevention trials, self-treatment and treatment trials have been applied to test Echinacea preparations. The majority of studies investigated whether Echinacea preparations taken after onset of cold symptoms shorten the duration of the common cold or decrease the severity of symptoms, compared with placebo. All prevention trials used similar primary outcomes, like the number of participants experiencing at least one cold episode, the number of participants experiencing more than one cold episode, severity scores, and cold duration in days. Among the self-treatment and treatment trials, methods for outcome measurements and the results actually presented varied substantially. This problem is due to the lack of well-developed and validated outcome measures in common cold research. Therefore, it would be desirable if available recommendations for outcome measures like WURSS (Wisconsin Upper Respiratory Symptom Survey), an evaluative illness-specific quality of life instrument, designed to assess the negative impact of the common cold, [11], [12] were commonly used.

Quality of Studies

The majority of trials included in all the described meta-analyses were of reasonable to good quality according to the Jadad criteria [13]. The median Jadad score in the recent Cochrane study reviewing 16 controlled clinical trials was 3.5 (range 0 to 5) and the median value for the Internal Validity Scale was 4.25 (range 0 to 6). The Cochrane review concluded that preparations, both alcoholic extracts and pressed juice, that are based primarily on the aerial parts of Echinacea purpurea might have beneficial effects on cold symptoms in adults if treatment is started early [7]. The meta-analysis by Shah et al. included two sets of studies: nine studies investigating whether Echinacea compounds prevent colds and seven studies investigating whether they shorten their duration. One minor, but potentially misleading error is made in the data of the study by Barrett et al. [14]. While the descriptive overview table of the Shah et al. study correctly displays that patients receiving Echinacea had longer cold episodes than patients in the placebo groups, the Forest plot (meta-analytic display) shows a non-significant superiority of the tested Echinacea product [15]. Nevertheless, even after correction, it can be stated that there is a significant improvement of common cold after taking Echinacea. In detail, Echinacea decreased the odds of developing the common cold by 58 % and the duration of a cold by 1.4 days [5].

The meta-analyses of three preventative trials using an experimental virus challenge model showed that all demonstrated at least a trend in favour of Echinacea. This may indicate that most available prevention trials did simply not include sufficient numbers of participants. After pooling of 3 induced rhinovirus prevention studies, the odds of experiencing a clinical cold were 55 % higher with placebo than with Echinacea [6].

Conclusions

As with most medications for the treatment of the common cold, the clinical data on Echinacea so far are not conclusive. There is a clear indication that preparations from the aerial parts and roots of Echinacea purpurea may be effective. However, more studies with precisely standardised products (pressed juices and tinctures) are necessary in various clinical settings, also for prevention. So far in preventative trials, only a trend in inhibition of the development and severity of colds could be demonstrated. Preparations from Echinacea angustifolia and E. pallida roots need further controlled clinical trials, in order to provide a better evidence for clinical efficacy.

In addition to studies with laboratory-measured biomarkers, also more studies on patient-oriented quality-of-life measures are needed [16]. The Jackson scale assesses eight symptoms, sneezing, nasal obstruction, nasal discharge, sore throat, cough, headache, chilliness and malaise, using a three- or four-point response range, but does not evaluate functional or quality-of-life items [17]. Therefore, the Wisconsin Upper Respiratory Symptom Survey (WURSS) was developed as an evaluative illness-specific quality-of-life outcomes instrument, to measure change over time in domains most important to cold sufferers [11], [12]. That means WURSS scores correlate better with general health-related quality-of-life. A recently published study using data from an induced rhinovirus (RV)-cold Echinacea trial clearly demonstrated a relation between questionnaire and laboratory parameters [12]. Both the Jackson and the WURSS scales correlate significantly with laboratory-assessed measures.

The results and information presented here should be a motivation to conduct larger prevention trials in the future. The WURSS-21 score, a short form of WURSS-44, which also includes functional and quality-of life domains, should be used as outcome measurement instrument, in regard to the estimated 74 participants needed to detect the minimal important difference in a two-armed clinical trial compared with 92 for the WURSS-44 (32 items assessing symptoms, 10 functional items and 2 global assessment items) and 124 participants for the Jackson score.

References

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• 13 Jadad A R, Moore R A, Carrol D, Jenkinson C, Reynolds D JM, Gavaghan D J. et al . Assessing the quality of reports of randomized trials: is blinding necessary?.  Control Clin Trials. 1996;  17 1-12
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Univ.-Prof. Dr. Rudolf Bauer

Institute of Pharmaceutical Sciences

Pharmacognosy

Karl-Franzens University Graz

Universitätsplatz 4

8010 Graz

Austria

Phone: +43-316-380-8700

Fax: +43-316-380-9860

Email: rudolf.bauer@uni-graz.at

References

• 1 Woodwell D A, Cherry D K. National ambulatory medical care survey: 2002 summary.  Adv Data. 2004;  346 1-44
  PubMedSearch in Google Scholar
• 2 Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis (Cochrane Review). The Cochrane Library, (1). Chichester; Wiley 2004
  Search in Google Scholar
• 3 Blumenthal M. Herb sales down 6 percent in mainstream market.  Herbal Gram. 2005;  66 63
  PubMedSearch in Google Scholar
• 4 Bauer R. Chemistry, analysis and immunological investigations of Echinacea phytopharmaceuticals. In: Wagner H, editor Immunomodulatory agents from plants. Basel, Boston, Berlin; Birkhäuser Verlag 1999: 41-88
  Search in Google Scholar
• 5 Shah S A, Sander S, White C M, Rinaldi M, Coleman C I. Evaluation of Echinacea for the prevention and treatment of the common cold: a meta-analysis.  Lancet Infect Dis. 2007;  7 473-80
  CrossrefPubMedSearch in Google Scholar
• 6 Schoop R, Klein P, Suter A, Johnston S L. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis.  Clin Ther. 2006;  28 174-83
  CrossrefPubMedSearch in Google Scholar
• 7 Linde K, Barrett B, Wölkart K, Bauer R, Melchart D. Echinacea for preventing and treating the common cold. The Cochrane Database of Systematic Reviews; Issue 1: 2006
  Search in Google Scholar
• 8 Melchart D, Linde K, Worku F, Bauer R, Wagner H. Immunmodulation with Echinacea - A systematic review of controlled clinical trials.  Phytomedicine. 1994;  1 245-54
  PubMedSearch in Google Scholar
• 9 Gwaltney JM J r, Hendley J O, Patrie J T. Symptom severity patterns in experimental common colds and their usefulness in timing onset of illness in natural colds.  Clin Infect Dis. 2003;  36 714-23
  CrossrefPubMedSearch in Google Scholar
• 10 Gagnier J J, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. CONSORT Group. Recommendations for reporting randomized controlled trials of herbal interventions: Explanation and elaboration.  J Clin Epidemiol. 2006;  59 1134-49
  CrossrefPubMedSearch in Google Scholar
• 11 Barrett B, Locken K, Maberry R, Schwamman J, Brown R, Bobula J. et al . The Wisconsin Upper Respiratory Symptom Survey (WURSS): a new research instrument for assessing the common cold.  J Fam Pract. 2002;  51 265-73
  PubMedSearch in Google Scholar
• 12 Barrett B, Brown R, Voland R, Maberry R, Turner R. Relations among questionnaire and laboratory measures of rhinovirus infection.  Eur Respir J. 2006;  28 358-63
  CrossrefPubMedSearch in Google Scholar
• 13 Jadad A R, Moore R A, Carrol D, Jenkinson C, Reynolds D JM, Gavaghan D J. et al . Assessing the quality of reports of randomized trials: is blinding necessary?.  Control Clin Trials. 1996;  17 1-12
  CrossrefPubMedSearch in Google Scholar
• 14 Barrett B P, Brown R L, Locken K, Maberry R, Bobula J A, D’Alessio D. Treatment of the common cold with unrefined Echinacea. A randomized, double-blind, placebo-controlled trial.  Ann Intern Med. 2002;  137 939-46
  CrossrefPubMedSearch in Google Scholar
• 15 Linde K. Do Echinacea products prevent and shorten the common cold?. Focus Complement Altern Ther, in press
  Search in Google Scholar
• 16 Gillespie E L, Coleman C I. The effect of Echinacea on upper respiratory infection symptom severity and quality of life.  Conn Med. 2006;  70 93-7
  PubMedSearch in Google Scholar
• 17 Jackson G G, Dowling H F, Muldoon R L. Present concepts of the common cold.  Am J Public Health. 1962;  52 940-5
  PubMedSearch in Google Scholar

Univ.-Prof. Dr. Rudolf Bauer

Institute of Pharmaceutical Sciences

Pharmacognosy

Karl-Franzens University Graz

Universitätsplatz 4

8010 Graz

Austria

Phone: +43-316-380-8700

Fax: +43-316-380-9860

Email: rudolf.bauer@uni-graz.at