Summarising the results of individual randomised controlled trials, if they are sufficiently homogenous, provides a more robust indication of the treatment effect. In a systematic review there should have been a rigorous and transparent methodology, ideally with a published protocol that has been peer reviewed before the review is undertaken such as the case for Cochrane reviews. Other systematic reviews largely rely on published evidence while Cochrane reviews will also attempt to identify unpublished data and so-called grey literature that is published outside traditional routes.
Timmer et al (2013) published an update of their 2008 review of Pelargonium sidoides extract for acute respiratory tract infections. They identified 10 studies, eight of which were included in meta-analyses.
Acute bronchitis in adults
Three studies were included that had a total of 746 adult patients with bronchitis. Two of the studies had used liquid preparation and one had used tablets of three differed concentrations of Pelargonium sidoides compared to placebo. There was high heterogeneity for all the primary outcomes. In the meta-analysis, the calculated pooled effects for failure to resolve the symptom of sputum showed superiority of Pelargonium with a Risk Ratio (RR) of 0.70 (95% CI 0.6 to 0.82, p<00001). In the subgroup analysis for tablets favoured Pelargonium over Placebo with a RR of 0.95 and a narrow confidence interval (0.91 - 0.99) for complete resolution of symptoms by day seven (p=009).
Acute bronchitis in children
Three trials with a total of 819 children with acute bronchitis were included. Similar to the adult analysis there was heterogeneity. Subgroup analysis showed efficacy for liquid Pelargonium over placebo for complete resolution of symptoms, RR 0.82 (95% CI 0.77 to 0.88) and cough, RR 0.82 (95% CI 0.76 to 0.88). This was not the case for the tablet formulation. The forest plot for resolution of symptoms by day seven can be accessed here.
Acute sinusitis
One study of 104 patients with acute sinusitis was included (Bachert, 2009). The analysis showed significant treatment effect in favour of Pelargonium for complete resolution of all symptoms by day 21, RR 0.43 (95% CI 0.30 to 0.62), nasal discharge (RR 0.21, 95% CI 0.11 to 0.40) and resolution of headaches (RR 0.23, 95% CI 0.12 to 0.44). This publication is discussed further on the Clinical Research page.
Common cold
One trial of 103 patients with the common cold was included (Lizogub, 2007). Analysis at seven days show now significant treatment effect but at 10 days there was significant effect in favour of Pelargonium (RR 0.41, 95% CI 0.29 to 0.60, p<0.00001).
The Timmer Cochrane review also examined the adverse events in 8 of the trails. The results will be discussed on the Safety and Adverse Drug Reactions page.
Kardos et al (2022)
Kardos et al (2022) published a systematic review and meta-analysis of the use of Pelargonium for acute cough and quality of life in patients with acute bronchitis and common cold. There were 11 randomised trials reported in 9 publications; seven of these trials were included in the Cochrane review by Timmer et al (2013).
Acute bronchitis in adults
The review included the same three trials as the Cochrane review but interestingly omitted the 30 mg arm of the three treatment arm trail of Matthys et al (2010). The pooled data of 373 adults that received active treatment (compared to 271 placebo) reported a mean treatment group difference of 0.89 points for cough intensity score change between baseline and seven days. In the pooled analysis, 88.7% of patients treated with Pelargonium showed at least a 50% reduction in cough intensity compared to 47.6% of the placebo group.
Quality of life (QoL) measures assessed using the EQ-5D questionnaire showed over 80% remission rates in the Pelargonium treated group where four out of five measures showed less than 65% remission rates. The EQ5-5D-3L questionnaire examines mobility, ability for self care and usual activities, pain and anxiety/depression. There were greater advantages in the treatment group over placebo for pain/discomfort and ability to to undertake usual activities.
In the trials of children and adolescents the treatment effects and QoL improvement over placebo were similar but the mean differences were of a lesser magnitude.
The common cold
The meta-analysis was undertaken of the participants (all adults) that were experiencing coughing at baseline, 345 in the treatment groups and 348 in placebo groups in a total of six trials.
The mean difference in change of cough intensity between baseline and day five was significantly greater (0.34 points) in the treatment group compared to placebo. In the pooled analysis, 56.8% of the Pelargonium treatment group showed a 50% reduction in cough intensity compared to 38.8% of the placebo group at day 5.
Matthys et al (2023)
A meta-analysis of four placebo controlled randomised trials by Matthys et al (2023) analysed the secondary outcome measure, ability to work in adults with acute bronchitis who received Pelargonium compared to placebo. There was a weighted mean difference of 1.73 sick days (95% CI 1.17 - 2.29 days) off with significantly fewer sick days in the Pelargonium group compared to placebo (p<0.00001).
The second analysis in the review looked at the number how were unable to work at baseline compared to at the end of the study. The risk ratio was 0.35 (95% CI 0.2 - 0.45; p<0.001) in favour of pelargonium. The proportion unable to work decreased to between 19% and 14% in the Pelargonium group compared to between 41% and 55% in the placebo group.
Schapowal et al (2019)
A meta-analysis of five placebo controlled RCTs by Schapowal et al (2019) using Pelargonium versus placebo for the common cold. The trials used the Cold Intensity Score (CIS) as the primary outcome which is a validated instrument taking the sum of ten cold-related symptoms including nasal drainage, nasal congestion, sore throat, headaches and fever. Each symptom is scored on a five point scale from 0 (not present) to 5 (very severe), the sum of the individual scores providing the CIS.
There was significant heterogeneity between the groups but there was a significant difference in the change of CIS from baseline to five days (p=0.01) and the complete remission of all symptoms at day 10 (p=0.04) in favour of Pelargonium. Paracetamol usage was significantly lower in the Pelargonium groups compared to placebo (p=0.04).
Interestingly, the change of the individual CIS symptoms from baseline to day five favoured the Pelargonium groups in general. Changes in the symptoms of sore throat, nasal congestion, sneezing, scratchy throat, hoarseness and cough were significant in the Pelargonium group.
Hoang et al (2023)
A systematic review and network meta-analysis by Hoang et al (2023) included 47 RCTs evaluating 18 herbal medicines including Pelargonium for the treatment of rhinosinusitis. The same Pelargonium trials that were included in the other systematic reviews were included in this one; the network meta-analysis allows comparison of multiple treatments for the comparative effectiveness. Ranking the herbal medicines Pelargonium was the most beneficial for symptom relief for the common cold. Significantly improved patient-important outcomes (HRQoL, symptoms) were reported in patients with common cold and rhinosinusitis for Pelargonium, Andrographis paniculate, Ceneole, Sinupret and Spicae aetheroleum.
Wagner et al (2015)
The systematic review of Wagner et al (2015) assessed the literature on herbal medicines for the symptom cough in respiratory tract infections. There were 11 RCTs identified, largely those also included in the Cochrane review by Timmer et al (2013) with one additional trial excluded from the Cochrane review. This review was also used for the development of the NICE guidance. Despite the slightly differing data extraction the treatment effects were broadly similar to the Cochrane review and showed moderate evidence of benefit for Pelargonium over placebo in adults and in children using the liquid preparation.
The review also examined the evidence for other herbal medicines. They concluded that there was strong evidence for Andrographis paniculata and ivy/primrose/thyme based preparations and limited evidence for Echinacea for treating cough symptoms.
Cochrane (previously known as the Cochrane Collaboration) is an international network with headquarters in the UK founded in 1993. It was founded by Sir Iain Chalmers in response to Archie Cochrane who was a strong advocate of randomised controlled clinical trials. Cochrane is for everyone who wishes to obtain the highest quality evidence to assist in making healthcare decisions, not just clinicians but patients, carers and policy makers too.
The distinctive Cochrane logo comprised of two C shapes originally represented the Cochrane Collaboration now represents global collaboration. The centre illustrates a forest plot of the the results from a landmark systematic review. This review examined the evidence for providing antenatal steroids to women at risk of preterm birth to accelerate foetal lung maturation. The horizontal lines represent the individual trials and the diamond the summary of all these trials clearly showing a benefit of the intervention; a simple intervention that has saved the lives of many premature babies.
Once you understand what to look for, forest plots from meta-analyses are very easy to follow and rapidly see the summary of the evidence.
Chang et al (2022) has produced a brief and useful guide to interpreting a forest plot. This video explains forest plots in the context of the steroid review used for the Cochrane logo.