Respiratory Infection

South African Geranium for Bronchitis in Children and Adolescents: Just What the Doctor Ordered?

Abstract & Commentary

By Craig Schneider, MD, Director of Integrative Medicine, Department of Family Medicine, Maine Medical Center in Portland. Dr. Schneider reports no financial relationships relevant to this field of study.

Source: Kamin W, et al. Treatment of acute bronchitis with EPs 7630: Randomized, controlled trial in children and adolescents. Pediatr Int 2012;54:219-226.

Acute bronchitis — inflammation of the large airways presenting with cough — is one of the most common diagnoses seen in primary care. Usually caused by viral infections, it is self-limited and antibiotics generally are not recommended. Safe and effective alternative treatments for this common condition would be a welcome addition for busy clinicians and their suffering patients.

The authors randomized 220 patients between the ages of 1 and 18 with acute bronchitis symptoms beginning less than 48 hours prior to assessment to receive either a standardized ethanolic root extract (1:8-10, 11% ethanol) of Pelargonium sidoides (South African geranium) designated EPs 7630 or a matched placebo. There were no significant demographic or anthropometric data differences between the groups. Over the next 7 days, patients ages 1-6 years received 10 drops three times daily (TID), ages 7-12 received 20 drops TID, and ages 13-18 received 30 drops TID. Investigators and patients were blinded to treatment. Examinations were performed at the first visit, between days 3-5, and again on day 7.

Investigator-rated change in bronchitis severity score (BSS) (total score for severity of cough, pulmonary rales, and dyspnea using a 5-point rating scale from absent to very severe) from day 0 to day 7 constituted the primary efficacy variable. Secondary variables included change in individual symptoms within the BSS, and change in general symptoms including lack of appetite, headache, vomiting, diarrhea, onset of treatment effect, health status, and quality of life using the FGK questionnaire (used in Germany to assess health status of children). Treatment outcomes were assessed by both patient (or caregiver) and investigator using the Integrative Medicine Outcomes Scale (IMOS), a 5-point rating scale (complete recovery, major improvement, slight-to-moderate improvement, no change, deterioration). Satisfaction with treatment was assessed using the Integrative Medicine Patient Satisfaction Scale, a 5-point rating scale (very satisfied, satisfied, undecided, dissatisfied, very dissatisfied) completed by patient or caregiver. Additional secondary endpoints included duration of bed rest and ability to attend kindergarten, school, or work. Investigators monitored adverse events, vital signs, and laboratory safety parameters.

All patients were included in safety, tolerability, and efficacy analysis using intention-to-treat principles. Only two patients dropped out of each group. Antibiotics eventually were prescribed in five patients treated with EPs 7630 and three in the placebo group.

BSS scores dropped by 4.4 ± 1.6 in the EPs 7630 group between day 0 and day 7, vs a drop of 2.9 ± 1.4 points in the placebo group (P < 0.0001, analysis of covariance). The results were significant in each age group. For cough and pulmonary rales, the mean reduction in BSS from day 0 to day 7 was greater in the EPS 7630 group (P < 0.0001, two-sided t-test, each, confidence interval 95%). Of the other general symptoms, only lack of appetite improved significantly in the EPs 7630 group (P = 0.0003, two-sided t-test). Patients and caregivers reported onset of treatment effect significantly earlier in the EPs 7630 group compared to placebo (P < 0.0001, two-sided Mantel-Haenszel ±-test). At day 7, the EPs 7630 group reported significantly better IMOS scores than placebo group (P < 0.0001, two-sided Mantel-Haenszel X2-test) with similar assessments by both patients and investigators. Satisfaction of patients receiving EPs 7630 also was significantly higher than placebo (P < 0.0001, two-sided Mantel-Haenszel X2-test).

Improvement of health status and quality of life as assessed by FKG improved for both groups, with improvement only statistically significant for the EPs 7630 group for the item “I am feeling ill” (P = 0.0485, two-sided t-test). At the beginning of the study, the authors report that no patients in the EPs 7630 group and only one in the placebo group was able to attend kindergarten, school, or work. By day 7, 64 patients (57.7%) in the EPs 7630 group, but only 19 patients (17.4%) of the placebo group were back to kindergarten, school, or work.

Three non-serious, adverse effects in two of the 111 patients in the EPs 7630 group were reported, and a causal relationship was excluded for each. “Only marginal group differences” were noted in clinical laboratory parameters, but no specifics were reported.

Commentary

Acute bronchitis is a clinical diagnosis that, although usually not serious, is an uncomfortable experience for patients and a frequent cause of lost days at school and work (for patients and their caregivers). If, as suggested by the authors, taking EPs 7630 speeds return to school and work as significantly as reported in this study, this could make an enormous positive socioeconomic impact if it were widely used.

This study appears well-designed and carefully conducted. Acknowledged weaknesses include use of outcomes that are subjective and measurement instruments that are not validated. EPs 7630 does possess documented plausible mechanisms of action for its use in treating bronchitis. These include stimulation of tumor necrosis factor and interleukin release, as well as enhanced interferon and natural killer cell activity, increased phagocytosis, and reduced bacterial adhesion.1 EPs 7630 is also reportedly mucolytic and improves cilia function in vitro.

The results of this study are consistent with most of the other published work looking at EPs 7630.2,3 However, as with most studies on this product, conflict of interest is apparent, with financial support for it coming directly from Dr. Willmar Schwabe GmbH & Co KG, Karlsruhe, Germany, the manufacturer of EPs 7630. The population studied was located in Russia and it is possible that patterns of infection, and illness behaviors including time before return to work and home care measures, may vary compared to those in other parts of the globe.

Although we do not know about long-term safety, the recommended 7-day course appears to be safe and well-tolerated. It is not yet known if EPs 7630 is safe to use in pregnancy or lactation, and thus it should not be recommended in this population.

There is widespread agreement in the health care community that routine antibiotic treatment is not recommended for uncomplicated acute bronchitis unless Bordetella pertussis is suspected. However, providers often feel pressured by patients and their caregivers to provide antibiotics, and this often becomes a time-consuming process of education if not a struggle that can lead to challenges in the provider-patient relationship. Safe and effective nonantibiotic treatments for common viral conditions would be a welcome addition for busy clinicians and their suffering patients.

In adults, symptomatic care with over-the-counter cough and cold preparations are often recommended, but we also know that such preparations (antitussives, antihistamines, decongestants, and their combinations) are not more effective than placebo in children. The FDA recommends these not be used at all in children younger than 2 years and supports not using them in children younger than 4 years of age as well.4

As we look for collaborative, nonantibiotic approaches to treating acute bronchitis that are acceptable to both provider and patient, that can reduce the risk of adverse effects of inappropriate treatment while limiting growth of antibiotic resistance, and that potentially can benefit the economy overall as patients and their caregivers are able to return to their productive lives sooner, South African geranium as EPs 7630 might be just what the doctor ordered.

References

1. Conrad A, et al. Extract of Pelargonium sidoides (EPs 7630) inhibits the interactions of group A-streptococci and host epithelia in vitro. Phytomedicine 2007;14(Suppl 6):52-59.)

2. Matthys H, et al. Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomized, double-blind, placebo-controlled trial. Phytomedicine 2003;10(Suppl 4):7-17.

3. Agbabiaka TB, et al. Pelargonium sidoides for acute bronchitis: A systematic review and meta-analysis. Phytomedicine 2008;15:378-385.

4. U.S. Food and Drug Administration. An important FDA reminder for parents: Do not give infants cough and cold products designed for older children. Available at: http://www.fda.gov/Drugs/ResourcesForYou/SpecialFeatures/ucm263948.htm. Accessed Dec. 13, 2012.