• 
• 

Three Part Question

In [children with upper respiratory tract infection] is treatment with [Echinacea purpurea] effective for [alleviating symptoms and shortening the course of URTI]?

Clinical Scenario

You are a paediatric specialist registrar on a Sunday late shift in the accident and emergency department. A 4 year old boy presents with a two day history of fever (maximum temperature 38.8°C) and clinical signs of an upper respiratory tract infection (URTI). At home, his mother gave regular paracetamol to treat his fever and extracts from ivy to alleviate the cough. She asks you about Echinacea purpurea therapy for her son's illness.

Search Strategy

Cochrane Database of Systematic Reviews
Pubmed
"Echinacea" AND ("respiratory infection" OR "cold"). Limits: "Randomized controlled trial" or "clinical trial". 15 hits, 7 relevant. "Echinacea" AND ("respiratory infection" OR "cold") AND ("children" OR "infants"). Limits: "Randomized controlled trial" or "clinical trial". 2 hits, 1 relevant. Embase: "Echinacea" AND "respiratory" AND "infection" AND "trial". No further relevant hits. "Echinacea" AND "respiratory" AND "infection" AND "children" AND "trial". No further relevant hits.

Search Outcome

Cochrane 1 hit

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Taylor et al, 2003	524 children randomised (age 2–11 years), 200 with 337 URTIs included in analysis received aerial EP extract versus 207 with 370 URTIs receiving placebo EP juice from dried pressed herbs. Children 2–5 years received 2x3.75 ml; 6–11 years received 2x5 ml until symptoms resolved (max. 10 days)	Randomised, double blind, placebo controlled trial	Duration of URTI:	Echinacea v placebo 9 v 9 days (p = 0.89)	No effect of treatment of URTI with EP in shortening duration or decreasing severity despite multiple subanalysis 95% CI: 8–10 days for durations Large sample size The only paediatric trial
			Severity of URTI (score):	33 v 33 (p = 0.69)
			Adverse effects (no.):	152 v 146 (p = 0.14)
Goel et al, 2004	282 adults (age 18–65 years) randomised, 128 with cold, 59 receiving EP extract. 69 placebo Extract from EP plants with 0.25 mg/ml alkamides + 2.5 mg/ml cichoric acid + 25 mg/ml polysaccharides, combined in 40% ethanol. 10x4 ml day 1; 4x4 ml days 2–7	Randomised, double blind, placebo controlled trial	Total daily symptom score:	Signif. decrease in symptom score by Echinacea (p<0.05)	Only relief/decrease of symptoms examined, no statistical power on duration of URTI 95% CI for total daily symptom score: 13.6–19.0 for EP 17.5–22.5 for placebo Large sample size
			Duration of 50% reduction of maximum symptom score (days)	4/5.5 (EP v placebo) (statistical significance not mentioned)
Yale et al, 2004	128 adults (age 18–62 years), presenting with acute sneezing or nasal discharge (common cold). 63 receiving aerial EP extract, 65 placebo Aerial EP extract in 100 mg capsules. 3x1 capsule until symptoms resolved (max. 14 days)	Randomised, double blind, placebo controlled trial	Duration of cold:	No signif. difference (p = 0.73)	No effect of EP treatment on duration or total symptoms. CI not mentioned Modest sample size
			Total symptom score:	No signif. difference (p = 0.29–0.90)
Barrett et al, 2002	148 adults (students, mean age 21 years), presenting with 2 of 15 listed cold symptoms. 73 receiving capsules of EP herb and root and EA root, 75 placebo Echinacea capsules containing EP herb (62 mg), EP root (62 mg) and EA root (123 mg). 6x4 capsules day 1; 3x4 capsules until symptoms resolved (max. 10 days)	Randomised, double blind, placebo controlled trial	Duration of cold:	Echinacea v placebo 6.27 v 5.75 days (95% CI –1.09 to 0.22 days)	No effect of a specific Echinacea mixture preparation on duration and severity of cold symptoms. Probands were healthy college students. 95% CI: –1.09 to 0.22 days for EP group Adjusted hazard ratio 1.24 (CI 0.8 to 1.78) Modest sample size
			Symptom severity:	No signif. difference
			Adverse effects (no.):	13 v 7 (no signif. difference)
Schulten et al, 2001,	80 adults (mean age 37.3/38.8 years), presenting first signs of common cold. 41 receiving EP juice, 39 placebo EP juice (pressed from fresh flowering purple cornflower). 2x5 ml for 10 days	Randomised, double blind, placebo controlled trial	Duration of illness (days):	Echinacea v placebo 6 v 9 (p = 0.0112)	Positive effect of EP, probands were company workers CI not mentioned Small sample size Drug company sponsored
			Area under the curve of symptoms:	36.18 v 51.63 (p = 0.008)
			Patients' subjective assessment (shorter duration of cold) (%):	61.0 v 28.2 (p = 0.007)
Lindenmuth et al, 2000,	95 adults (age 24–62 years), presenting early symptoms of cold. 48 receiving EP tea preparation, 47 placebo tea Tea bags of leaves, flowers and stems of EP and EA plus dry extract of EP roots (6:1). In combination 1.275 mg of dried herb + root per tea bag. 5–6 tea bags day 1, every following day one tea bag less	Randomised, double blind, placebo controlled trial	Subjective relief of symptoms (score):	Echinacea v placebo 4.125 v 2.787 (p<0.001).	Echinacea tea preparation has only positive effect in relief of symptoms CI not mentioned. Small sample size Authors' interpretation of the results controversial
			Duration of symptoms (days):	4.333 v 2.34 (p<0.001)
			Duration of subjective change of symptoms (days):	3.854 v 2.297 (p<0.001)
Brinkeborn et al, 1999,	559 adults recruited, 246 treated (mean age 40–42 years). 55 receiving EP extract, 64 EP concentrate, 63 EP special extract, 64 placebo Echinacea tablets: EP extract (6.78 mg; 95% herb, 5% roots); EP concentrate (48.27 mg; 95% herb, 5% roots); EP extract (29.6 mg; 100% roots). 3x2 tablets until symptoms resolved (max. 7 days)	Randomised, double blind, placebo controlled trial	Reduction of complaint index (based on symptoms by doctors' records):	Signif. reduction of index by EP extract (p = 0.02) and concentrate (p = 0.003) v placebo	EP concentrate only slightly more effective than EP extract despite 7-fold higher dosage. No effect by EP roots-based preparation Effects on duration of cold not examined CI not mentioned Small subgroup samples
			Reduction of complaint index by patients' diaries:	Signif. reduction of index by EP extract (p = 0.032) and concentrate (p = 0.01) v placebo
			Adverse effects:	More AE in the EP special extract (not signif.)

Comment(s)

In recent years, alternative medicines have gained much popularity. According to a recent survey, more than one third of the US population consumes herbal medicines regularly (Islam). Reasons for the surge of herbal remedies include the widely assumed good tolerance of "natural" products and a supposed lack of side effects, a belief often paired with scepticism towards the efficacy of "conventional" medicine. Particularly in paediatric medicine, it seems in vogue to treat common childhood ailments using herbal medicines. Among the most commonly used remedies are Echinacea preparations, constituting approx. 10% of the total US market in herbal medicine, with annual sales worth over US$300 million(Islam). Complaints about an URTI account for about 40% of visits to paediatricians during winter months, and herbal substances are increasingly being prescribed by medical practitioners despite a lack of convincing proof of their effectiveness or safety(Caruso). In particular, Echinaceás attributed immune modulating effects may not only be beneficial: Echinacea possibly reduces the effectiveness of corticosteroids, commonly used by asthmatics and for treating viral induced wheeze, and can cause hypersensitivity reactions in susceptible individuals(Huntley, Niggemann). Treatment of the common cold in children with Echinacea has only been investigated in one randomised, double blind, placebo controlled trial: Taylor et al examined the efficacy and safety of Echinacea purpurea in children with URTI. The authors studied a large cohort by using a stringent methodology, but the results failed to show an influence on duration of illness or severity of symptoms. To further elucidate our clinical question, we extended our search to treatment trials in the adult population. A Cochrane review about Echinacea treatment, published in 1999, found no definite treatment effect and criticises methodological inconsistencies among the studies available(Melchart). We reviewed six recent randomised controlled trials of adults receiving Echinacea treatment for symptoms of URTI. Neither the study populations, nor the preparations of Echinacea investigated in the trials were standardised, a fact that complicates the comparability of the results. The results are inconsistent; trials with a larger number of individuals failed to show a significant effect of Echinacea treatment, whereas smaller trials did document positive effects. Treatment with Echinacea purpurea was perceived as beneficial by a number of individuals, possibly due to the placebo effect. Currently, there is a lack of evidence on the efficacy of Echinacea purpurea, especially in paediatric patients. Under the present circumstances, the use of Echinacea as a treatment for URTI cannot be suggested as being effective. In particular, Echinacea should be not be taken by patients with chronic immune mediated disease on treatment with corticosteroids and those with allergy to ragweed and related allergens (Huntley, Niggemann).

Editor Comment

EP, Echinacea purpurea; EA, Echinacea angustifolia, CI, confidence interval.

Clinical Bottom Line

There is currently no evidence for the efficacy of Echinacea purpurea in the treatment of children with upper respiratory tract infections. (Grade A) Echinacea should be avoided by patients who receive corticosteroids and by those with allergy to ragweed and related allergens. (Grade B)

References

1. Taylor JA, Weber W, Standish L. et al. Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. JAMA 2003;290:2824–30.
2. Goel V, Lovlin R. Barton R. et al. Efficacy of a standardized Echinacea preparation (Echinilin TM) for the treatment of the common cold: a randomised, double-blind, placebo-controlled trial. J Clin Pharm Ther 2004;29:75–83.
3. Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med 2004;164:1237–41.
4. Barrett BP, Brown RL, Locken K. et al. Treatment of the common cold with unrefined Echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002;137:939–46.
5. Schulten B, Bulitta M, Ballering-Bruhl B. et al. Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomized, double-blind clinical trial. Arzneimittelforschung 2001;51:563–8.
6. Lindenmuth GF, Lindenmuth EB. The efficacy of Echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study. J Altern Complement Med 2000;6:327–34.
7. Brinkeborn RM, Shah DV. Degening FH. Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial. Phytomedicine 1999;6:1–5.
8. Melchart D. Linde K. Worku F. et al. Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1995;1:145–60.
9. Stimpel M, Proksch A. Wagner H. et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845–9.
10. Melchart D, Linde K, Fischer P. et al. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev 2000;2:CD000530.
11. Islam J, Carter R. Use of Echinacea in upper respiratory tract infection. South Med Journal 2005;98:311–18.
12. Caruso T, Gwaltney JM. Treatment of the common cold with echinacea: a structured review. CID 2005;40:807–10.
13. Huntley AL, Thompson Coon J. Ernst E. The safety of herbal medicinal products derived from Echinacea species: a systematic review. Drug Saf 2005;28:387–400.
14. Niggemann B. Gruber C. Side-effects of complementary and alternative medicine. Allergy 2003;58:707–16.