Brief overview: Current evidence suggests that Echinacea supplementation may decrease the duration and severity of acute respiratory tract infections; however, no studies using Echinacea in the prevention or treatment of conditions similar to COVID-19 have been identified. Few adverse events were reported, suggesting that this herbal therapy is reasonably safe. Because Echinacea can increase immune function, there is a concern that it could worsen over-activation of the immune system in cytokine storm; however, clinical trials show that Echinacea decreases levels of immune molecules involved in cytokine storm. Verdict: Echinacea supplementation may assist with the symptoms of acute respiratory infections (ARI) and the common cold, particularly when administered at the first sign of infection; however, no studies using Echinacea in the prevention or treatment of conditions similar to COVID-19 have been identified. Previous studies have reported that Echinacea may decrease the severity and/or duration of ARI when taken at the onset of symptoms. The studies reporting benefit used E. purpurea or a combination of E. purpurea and E. angustifolia containing standardized amounts of active constituents. Few adverse events from the use of Echinacea were reported, suggesting that this herbal therapy is reasonably safe. No human trials could be located reporting evidence of cytokine storm when Echinacea was used for up to 4 months. When assessing all human trials which reported changes in cytokine levels in response to Echinacea supplementation, the results were largely consistent with a decrease in the pro-inflammatory cytokines that play a role in the progression of cytokine storm and Acute Respiratory Distress Syndrome (ARDS), factors that play a significant role in the death of COVID-19 patients. While there is currently no research on the therapeutic effects of Echinacea in the management of cytokine storm, this evidence suggests that further research is warranted.
Brief overview: Based on the evidence identified in this rapid review, Hedera helix preparations and herbal complex preparations including H. helix may be a therapeutic option for treating early symptoms of respiratory tract infections. The best effectiveness for H. helix preparations has been proven for coughing, as an expectorant and to reduce the frequency and intensity of cough. Only weak evidence was found for all other researched symptoms. Both adults and children tolerate H. helix well. Currently, there is insufficient evidence to recommend the use of this supplement in the treatment or prevention of COVID-19. However, the current evidence justifies further research to better understand its applicability in coronavirus infections. Verdic: tCurrent evidence suggests H. helix may improve the frequency and intensity of cough associated with viral respiratory infection. The overall applicability of additional findings is limited by the poorly defined outcome measures employed. However, studies focused explicitly on expectoration did report an increased conversion from dry to productive cough, and an improvement in expectoration amount, consistency and colour. These effects may be explained by a related finding of reduced oropharyngeal congestion and improved inflammatory markers (erythrocyte sedimentation rate and c-reactive protein). A decrease in frequency of night cough and respiratory pain was also reported, as was improved sleep quality and reduced cough-related sleep disturbance. Some studies also measured general respiratory tract infection symptoms and identified clinical improvement or resolution of fever, fatigue, sore throat, sneezing, wheezing, nasal congestion, post-nasal drip and body-ache. A reduced need for antibiotic prescriptions was also identified. While not consistently reported, the majority of studies also found H. helix reduced the overall severity of viral bronchitis and related conditions. Tolerability was rated as between ‘good’ and ‘high’. Adverse events were rare or non-existent in almost all studies, and those that were reported were defined as non-serious and not drug-related.
Echinacea vermindert het risico op recidiverende infecties en complicaties van de ademhalingswegen: een meta-analyse van gerandomiseerde gecontroleerde proeven
BACKGROUND: Echinacea plant preparations (family Asteraceae) are widely used in Europe and North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and the addition of other components.
OBJECTIVES: To assess whether there is evidence that Echinacea preparations are effective and safe compared to placebo in the prevention and treatment of the common cold.
SEARCH METHODS: We searched CENTRAL 2013, Issue 5, MEDLINE (1946 to May week 5, 2013), EMBASE (1991 to June 2013), CINAHL (1981 to June 2013), AMED (1985 to February 2012), LILACS (1981 to June 2013), Web of Science (1955 to June 2013), CAMBASE (no time limits), the Centre for Complementary Medicine Research (1988 to September 2007), WHO ICTRP and clinicaltrials.gov (last searched 5 June 2013), screened references and asked experts in the field about published and unpublished studies.
SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing mono-preparations of Echinacea with placebo.
DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed eligibility and trial quality and extracted data. The primary efficacy outcome was the number of individuals with at least one cold in prevention trials and the duration of colds in treatment trials. For all included trials the primary safety and acceptability outcome was the number of participants dropping out due to adverse events. We assessed trial quality using the Cochrane 'Risk of bias' tool.
MAIN RESULTS: Twenty-four double-blind trials with 4631 participants including a total of 33 comparisons of Echinacea preparations and placebo met the inclusion criteria. A variety of different Echinacea preparations based on different species and parts of plant were used. Evidence from seven trials was available for preparations based on the aerial parts of Echinacea purpurea.
Ten trials were considered to have a low risk of bias, six to have an unclear risk of bias and eight to have a high risk of bias. Ten trials with 13 comparisons investigated prevention and 15 trials with 20 comparisons investigated treatment of colds (one trial addressed both prevention and treatment).
Due to the strong clinical heterogeneity of the studies we refrained from pooling for the main analysis. None of the 12 prevention comparisons reporting the number of patients with at least one cold episode found a statistically significant difference. However a post hoc pooling of their results, suggests a relative risk reduction of 10% to 20%. Of the seven treatment trials reporting data on the duration of colds, only one showed a significant effect of Echinacea over placebo. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups.
AUTHORS' CONCLUSIONS: Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products: the results of individual prophylaxis trials consistently show positive (if non-significant) trends, although potential effects are of questionable clinical relevance.
BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Non-prescription, over-the-counter (OTC) medicines are frequently recommended as a first-line treatment, but there is little evidence as to whether these drugs are effective.
OBJECTIVES: To assess the effects of oral OTC cough preparations for acute cough in children and adults in community settings.
SEARCH METHODS: We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3 2014), EMBASE (January 1974 to March 2014), CINAHL (January 2010 to March 2014), LILACS (January 2010 to March 2014), Web of Science (January 2010 to March 2014) and the UK Department of Health National Research Register (March 2010).
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in community settings. We considered all cough outcomes; secondary outcomes of interest were adverse effects.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened potentially relevant citations, extracted data and assessed study quality. We performed quantitative analysis where appropriate.
MAIN RESULTS: Due to the small numbers of trials in each category, the limited quantitative data available and the marked differences between trials in terms of participants, interventions and outcome measurement, we felt that pooling of the results was inappropriate.
We included 29 trials (19 in adults, 10 in children) involving 4835 people (3799 adults and 1036 children). All studies were placebo-controlled RCTs. However, assessment of the risk of bias of the included studies was limited by poor reporting, particularly for the earlier studies.
In the adult studies, six trials compared antitussives with placebo and had variable results. Three trials compared the expectorant guaifenesin with placebo; one indicated significant benefit, whereas the other two did not. One trial found that a mucolytic reduced cough frequency and symptom scores. Two studies examined antihistamine-decongestant combinations and found conflicting results. Four studies compared other combinations of drugs with placebo and indicated some benefit in reducing cough symptoms. Three trials found that antihistamines were no more effective than placebo in relieving cough symptoms.
In the child studies, antitussives (data from three studies), antihistamines (data from three studies), antihistamine-decongestants (two studies) and antitussive/bronchodilator combinations (one study) were no more effective than placebo. No studies using expectorants met our inclusion criteria. The results of one trial favoured active treatment with mucolytics over placebo. One trial tested two paediatric cough syrups and both preparations showed a 'satisfactory response' in 46% and 56% of children compared to 21% of children in the placebo group. One new trial indicated that three types of honey were more effective than placebo over a three-day period.
Twenty-one studies reported adverse effects. There was a wide range across studies, with higher numbers of adverse effects in participants taking preparations containing antihistamines and dextromethorphan.
AUTHORS' CONCLUSIONS: The results of this review have to be interpreted with caution because the number of studies in each category of cough preparations was small. Availability, dosing and duration of use of over-the-counter cough medicines vary significantly in different countries. Many studies were poorly reported making assessment of risk of bias difficult and studies were also very different from each other, making evaluation of overall efficacy difficult. There is no good evidence for or against the effectiveness of OTC medicines in acute cough. This should be taken into account when considering prescribing antihistamines and centrally active antitussive agents in children; drugs that are known to have the potential to cause serious harm.
BACKGROUND: Pelargonium sidoides (P. sidoides), also known as Umckaloabo, is a herbal remedy thought to be effective in the treatment of acute respiratory infections (ARIs).
OBJECTIVES: To assess the efficacy and safety of P. sidoides for the treatment of ARIs in children and adults.
SEARCH METHODS: In April 2013 we searched MEDLINE, Journals@Ovid, The Cochrane Library, Biosis Previews, Web of Science, CINAHL, CCMed, XToxline, Global Health, AMED, Derwent Drug File and Backfile, IPA, ISTPB + ISTP/ISSHP, EMBASE, Cambase, LILACS, PubMed component "Supplied by Publisher", TRIPdatabase, the publisher databases: Deutsches Ärzteblatt, Thieme, Springer, ScienceDirect from Elsevier. We conducted a cited reference search (forward) in Web of Science of relevant papers for inclusion. In addition we searched the study registries ClinicalTrials.gov, Deutsches Register klinischer Studien DRKS (German Clinical Trials Register), International Clinical Trials Registry Platform (ICTRP) - WHO ICTRP, Current Controlled Trials and EU Clinical Trials Register.
SELECTION CRITERIA: Double-blind, randomized controlled trials (RCTs) examining the efficacy of P. sidoides preparations in ARIs compared to placebo or any other treatment. Complete resolution of all symptoms was defined as the primary outcome; in addition, we examined resolution of predefined key symptoms.
DATA COLLECTION AND ANALYSIS: At least two review authors (AT, JG, WK) independently extracted and quality scored the data. We performed separate analyses by age group and disease entity. Subanalysis considered type of preparation (liquid, tablets). We examined heterogeneity using the I(2) statistic. We calculated pooled risk ratios (RR) using a fixed-effect model if heterogeneity was absent (I(2) < 5%; P > 0.1), or a random-effects model in the presence of heterogeneity. If heterogeneity was substantial (I(2) > 50%; P < 0.10), a pooled effect was not calculated.
MAIN RESULTS: Of 10 eligible studies eight were included in the analyses; two were of insufficient quality. Three trials (746 patients, low quality of evidence) of efficacy in acute bronchitis in adults showed effectiveness for most outcomes in the liquid preparation but not for tablets. Three other trials (819 children, low quality of evidence) showed similar results for acute bronchitis in children. For both meta-analyses, we did not pool sub totals due to relevant heterogeneity induced by type of preparation.One study in patients with sinusitis (n = 103 adults, very low quality of evidence) showed significant treatment effects (complete resolution at day 21; RR 0.43, 95% confidence interval (CI) 0.30 to 0.62). One study in the common cold demonstrated efficacy after 10 days, but not five days (very low quality of evidence). We rated the study quality as moderate for all studies (unvalidated outcome assessment, minor attrition problems, investigator-initiated trials only). Based on the funnel plot there was suspicion of publication bias.There were no valid data for the treatment of other acute respiratory tract infections. Adverse events were more common with P. sidoides, but none were serious.
AUTHORS' CONCLUSIONS: P. sidoides may be effective in alleviating symptoms of acute rhinosinusitis and the common cold in adults, but doubt exists. It may be effective in relieving symptoms in acute bronchitis in adults and children, and sinusitis in adults. The overall quality of the evidence was considered low for main outcomes in acute bronchitis in children and adults, and very low for acute sinusitis and the common cold. Reliable data on treatment for other ARIs were not identified.
Inleiding. Onder niet-antibiotica hoest middelen, kruidenpreparaten met extracten van de bladeren van de klimop (Hedera helix) genieten een grote populariteit. Doelstelling Een systematische review naar de effectiviteit en verdraagbaarheid van klimop voor acute bovenste luchtweginfecties (bovensteluchtweginfecties) te beoordelen. Methoden. Er is gezocht naar gerandomiseerde gecontroleerde studies (RCT's), gerandomiseerd gecontroleerde klinische studies en observationele studies ter evaluatie van de werkzaamheid van klimop voorbereidingen voor acute bovensteluchtweginfecties. Onderzoek kwaliteit werd beoordeeld door de Jadad score of de EPHPP tool. Resultaten. 10 subsidiabele studies werden geïdentificeerd rapportage over 17463 onderwerpen. Studies waren heterogeen van opzet en de uitvoering, 2 waren RCT's. Drie studies geëvalueerd een combinatie van klimop en tijm, 7 studies onderzocht monopreparations van klimop. Slechts een RCT (n = 360) het onderzoeken van een klimop / tijm combinatie gebruik gemaakt van een placebo-controle en gaf een statistisch significante superioriteit in het verminderen van de frequentie en de duur van de hoest. Alle andere studies ontbreekt een placebo-controle en vertoont ernstige methodologische tekortkomingen. Ze concluderen dat klimop-extracten effectief zijn voor het verminderen van de symptomen van URTI. Conclusie. Hoewel alle studies melden dat ivy extracten effectief zijn om de symptomen van URTI verminderen, is er geen overtuigend bewijs als gevolg van ernstige methodologische tekortkomingen en het gebrek aan placebo controles. De combinatie van klimop en tijm zou efficiënter zijn maar moet de bevestiging.
OBJECTIVE: To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults.
QUALITY OF EVIDENCE: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included.
MAIN MESSAGE: For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold.
CONCLUSION: Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research.
Brief overview: Current evidence suggests that Echinacea supplementation may decrease the duration and severity of acute respiratory tract infections; however, no studies using Echinacea in the prevention or treatment of conditions similar to COVID-19 have been identified. Few adverse events were reported, suggesting that this herbal therapy is reasonably safe. Because Echinacea can increase immune function, there is a concern that it could worsen over-activation of the immune system in cytokine storm; however, clinical trials show that Echinacea decreases levels of immune molecules involved in cytokine storm. Verdict: Echinacea supplementation may assist with the symptoms of acute respiratory infections (ARI) and the common cold, particularly when administered at the first sign of infection; however, no studies using Echinacea in the prevention or treatment of conditions similar to COVID-19 have been identified. Previous studies have reported that Echinacea may decrease the severity and/or duration of ARI when taken at the onset of symptoms. The studies reporting benefit used E. purpurea or a combination of E. purpurea and E. angustifolia containing standardized amounts of active constituents. Few adverse events from the use of Echinacea were reported, suggesting that this herbal therapy is reasonably safe. No human trials could be located reporting evidence of cytokine storm when Echinacea was used for up to 4 months. When assessing all human trials which reported changes in cytokine levels in response to Echinacea supplementation, the results were largely consistent with a decrease in the pro-inflammatory cytokines that play a role in the progression of cytokine storm and Acute Respiratory Distress Syndrome (ARDS), factors that play a significant role in the death of COVID-19 patients. While there is currently no research on the therapeutic effects of Echinacea in the management of cytokine storm, this evidence suggests that further research is warranted.
