Pelargonium sidoides for Treatment of Acute Bronchitis
By Tina Sindwani, MD, Dr. Sindwani is a Fellow in the Program of Integrative Medicine, University of Arizona, Tucson; she reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Acute bronchitis is among the top 10 conditions leading patients to seek medical care in the United States.1 This respiratory illness results in a large amount of missed work days, and usually lasts for about two weeks. The pathophysiology of the condition appears to be related to some form of bronchial epithelial injury, resulting in inflammation, mucus production, and airway hyperresponsiveness.
The diagnosis of bronchitis is based on clinical findings alone, as there is no "gold standard" test at this time. Cough is the most common symptom, and can be accompanied by any number of additional signs and symptoms including sputum production, dyspnea, wheezing, chest pain, fever, hoarseness, malaise, and/or abnormal lung findings on auscultation. Pneumonia can often be ruled out by evaluation of vital signs (heart rate < 100 bpm, respiratory rate < 24, and temperature < 38° C make pneumonia less likely).
Antibiotics have been shown to be only modestly beneficial, at best.1-5 They do not appear to significantly shorten disease course or the number of missed work days, and their deleterious effects may outweigh their benefits (gastrointestinal upset, allergic reactions, and promotion of drug-resistant bacterial strains).2-6 Smokers do not appear to acquire any additional benefit from antibiotics over nonsmokers.7 In fact, the vast majority of acute bronchitis cases are thought to originate from viral infections, such as respiratory syncytial virus, adenovirus, echovirus, influenza, parainfluenza, entero-virus, and coxsackie virus.1,6,8
Nevertheless, up to 70% patients who are diagnosed with acute bronchitis are treated with antibiotics by primary care physicians. Other treatments commonly used include inhaled bronchodilators and antitussives. Due to the high prevalence of acute bronchitis and the frequency of missed work days resulting from it, an herbal alternative to antibiotics, with few adverse side effects and equal or better symptom relief, could be very useful. This review will address the potential effectiveness of Pelargonium sidoides root extract for the treatment of acute bronchitis, as a potential alternative to antibiotics.
Background/Mechanism of Action
Pelargonium sidoides, also known as the South African geranium, is a perennial flowering plant whose root extracts have been used traditionally by the native populations of Southern Africa for treatment of gastrointestinal and respiratory ailments. Several studies have evaluated its use as a therapeutically effective agent for treatment of tonsillopharyngitis9 and bronchitis;6,10 in addition, in vitro studies have revealed potential antiparasitic,11 antibacterial,12 and antimycobacterial activity.13 One randomized double-blind placebo-controlled trial demonstrated the efficacy of a pelargonium preparation for treatment of acute non-group A beta-hemolytic streptococcus tonsillopharyngitis in children.9
The mechanism of action of the root extract remains unclear; however, in vitro studies suggest that the active constituents include coumarins (e.g., umckalin) and tannins (e.g., catechin, gallocatechin, gallic acid), which seem to exhibit immunomodulatory and antimicrobial activities. The immunomodulatory actions appear to be mediated at least in part by an increase in release of tumor necrosis factor and nitric oxide, as well as stimulation of natural killer cell and interferon activity.10,11,13 It is also hypothesized that a component of the root extract functions to prevent adhesion of bacteria and viruses to the surface of the host cell. One study demonstrated that P. sidoides root extract significantly increased ciliary beat frequency of in vitro ciliated cell cultures of human nasal epithelium. These findings suggest a mechanism of action related to promotion of mucociliary clearance as well.14
The most commonly used form of P. sidoides in research trials has been EPs 7630. EPs 7630 has been used for some time in the treatment of ear, nose, and throat, and respiratory tract infections in Germany, Mexico, Russia, the Ukraine, and the Baltic states.
Clinical Studies
A recent randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of EPs 7630 compared with placebo for the treatment of acute bronchitis.6 Four hundred sixty-eight adult male and female subjects from outpatient care settings diagnosed with acute bronchitis, with symptom onset in the previous 48 hours, and Bronchitis Severity Scores (BSS) ≥ 5 were recruited. BSS is used to assess cough, sputum, rales/rhonchi, chest pain with coughing, and dyspnea using a 5-point scale. Subjects were randomized to receive 30 drops of EPs 7630 three times daily (4.5 mL/d) for seven days or a matched placebo. The investigational agent was dispensed in 50 mL bottles, containing 80 g EPs 7630, which corresponds to 8 g of plant material and 20 g of glycerol (85%). Acetaminophen was allowed for fever higher than 39° C.
The primary outcome measure was the change in BSS on day 7 compared with baseline. Secondary outcome measures included: other response criteria based on BSS, Integrative Medicine Outcomes Scale score, onset of treatment effect, amount of acetaminophen consumption, change in individual symptoms of bronchitis, results of health-related quality-of-life questionnaires, and questions using the Integrative Medicine Patient Satisfaction Scale. Blinded investigators performed controlled follow-up exams twice, once on days 3, 4, or 5, and once on day 7. On these days, the patient's clinical status was evaluated, the patient's symptom diary was reviewed, acetaminophen consumption was documented, and adverse events were recorded.
Upon final assessment on day 7, it was noted that the BSS had been reduced by 5.9 ± 2.9 in the EPs 7630 group, and by 3.2 ± 4.1 in the placebo group, compared with baseline BSS (P < 0.0001). This difference in improvement was apparent as early as the first follow-up visit (day 3-5). Patients in the EPs 7630 group were able to return to work nearly two days earlier than patients in the placebo group. Only 16% of subjects in the EPs 7630 group were unable to work at day 7, compared with 43% in the placebo group (P < 0.0001). Cough disappeared or improved in 89.2% of subjects in the investigational group, but only in 56.6% of the patients in the control group (P < 0.0001). Sputum production decreased or resolved in 66% of participants in the EPs 7630 group vs. 47.7% of subjects in the placebo group (P < 0.0002). On day 7, fever had disappeared in 96.9% of the patients receiving EPs 7630 and in 58.4% of the participants receiving placebo (P < 0.0001).
Adverse events, all described as nonserious by the investigators, were reported at about equal rates in both groups (8.6% in the EPs 7630 group and 6.8% in the placebo group). These included mostly ear, nose, throat, and respiratory complaints, perhaps related more to the underlying illness, and mild gastrointestinal complaints.
A smaller randomized, double-blind, placebo-controlled trial was also performed to evaluate efficacy and safety of EPs 7630 compared with placebo in management of acute bronchitis.10 One hundred twenty-four subjects older than 18 years of age from six urban Russian primary care clinics with a diagnosis of acute bronchitis, BSS ≥ 5, and duration of complaints ≥ 48 hours were recruited. Primary outcome measure was the magnitude of change in BSS at day 7. Other outcome measures included BSS < 5 at the end of the study, decrease in BSS ≥ 5 during the study, onset of treatment effect, acetaminophen consumption, changes in individual symptoms of BSS, health status of patient based on health-related quality-of-life questionnaire, score on Integrative Medicine Outcome scale, and satisfaction with treatment based on Integrative Medicine Patient Satisfaction Scale. Screening laboratory tests were obtained including leukocyte count, erythrocyte sedimentation rate, GGT, AST, and ALT.
At baseline, patients were given a symptom diary and a 50 mL bottle containing either EPs 7630 (n = 64) or a matched placebo (n = 60). Patients were instructed to take 30 drops three times daily (4.5 mL/d) 30 minutes before or after meals from day 0 to day 7. Acetaminophen 500 mg was allowed for fever 39° C or higher. Follow-up examination by blinded investigators occurred twice, once on days 3-5, and once on day 7. Evaluation of patient's clinical status, review of patient's symptom diary, documentation of acetaminophen and study medication consumption, and notation of change in concomitant medications or occurrence of adverse events took place on each of these follow-up visits.
A total of seven patients (three from the treatment group and four from the placebo group) dropped out due to lack of efficacy, violation of selection criteria, need for concomitant medications, or freedom from symptoms. The decrease in BSS on day 7 in the EPs 7630 group was 7.2 ± 3.1 vs. 4.9 ± 2.7 in the placebo group (P < 0.0001). On day 7, the rate of complete recovery for each individual symptom of the BSS was noted to be higher in the EPs 7630 group. The onset of treatment effect was noted by 68.8% patients receiving EPs 7630 on day 4, but only in 33.3% subjects receiving placebo (P < 0.0001). Based on questionnaires, 79.7% patients in the EPs 7630 group were satisfied with their treatment, whereas 43.3% of those in the placebo group were satisfied (P < 0.0001). With regard to health-related quality of life, scores for usual activities and mobility were notably higher in the EPs 7630 group compared with placebo at the end of the study.
Fifteen of 64 participants in the experimental group and 10 of 60 patients in the placebo group reported adverse events; however, all were described as nonserious. The authors concluded that EPs 7630 is superior to placebo in treatment of adults with acute bronchitis, in whom antibiotic therapy is not clearly indicated.
Adverse Effects and Contraindications
Based on the above studies, P. sidoides root extract appears to be a safe and well-tolerated treatment for acute bronchitis in adults at a dose of 4.5 mL/d for up to seven days. Only mild gastrointestinal, ear, nose, throat, and respiratory complaints were reported at this dosage. At this time, there are no known contraindications or drug interactions for the root extract of P. sidoides. However, it should be avoided in pregnant and lactating women until further data become available.
Dosage and Formulation
EPs 7630, an ethanolic root extract manufactured by Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany, and registered by ISO Pharmaceuticals, Ettlingen, Germany, is the standardized formulation commonly used in research trials of P. sidoides. A homeopathic formulation of P. sidoides known as Umcka ColdCare® is also available in the United States from Nature's Way. The dose studied in adults for acute bronchitis is 4.5 mL/d, as 30 drops three times daily, for seven days.6,10 For children, a dose of 3 mL/d, as 20 drops three times daily, for seven days, has been used for treatment of beta-hemolytic streptococcal tonsillopharyngitis.9
Conclusion
Based on these two well-conducted studies, EPs 7630, a P. sidoides root extract, is more effective than placebo in reducing symptoms of bronchitis after seven days of treatment. Results were statistically significant, and adverse events were described as nonserious. In addition, those patients taking EPs 7630 were able to return to work or resume usual activities sooner than those taking placebo. Patient satisfaction was higher in the EPs 7630 group, as measured in one study.
Recommendation
Although there is no obvious benefit from treatment with antibiotics in most cases of acute bronchitis, many physicians continue to prescribe them. In adult patients diagnosed with acute bronchitis with symptom onset within the prior 48 hours and without clear indication for antibiotics, P. sidoides root extract seems to be a safe and effective treatment alternative. Although this conclusion is based on only two studies, the agent's relatively benign side-effect profile compared with antibiotics and its ability to allow patients to resume usual activities sooner than placebo make it a viable treatment option that is worth considering. Further studies are warranted to confirm the efficacy and safety of P. sidoides root extract for treatment of acute bronchitis, but the evidence to date appears promising.
References
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10. Chuchalin AG, et al. Treatment of acute bronchitis in adults with a Pelargonium sidoides preparation (EPs 7630): A randomized, double-blind, placebo-controlled trial. Explore (NY) 2005;1:437-445.
11. Kayser O, et al. Immunomodulatory principles of Pelargonium sidoides. Phytother Res 2001;15:122-126.
12. Kayser O, Kolodziej H. Antibacterial activity of extracts and constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Medica 1997;63:508-510.
13. Kolodziej H, et al. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 2003;10(Suppl 4):18-24.
14. Neugebauer P, et al. A new approach to pharmacological effects on ciliary beat frequency in cell cultures—exemplary measurements under Pelargonium sidoides extract (EPs 7630). Phytomedicine 2005;12:46-51.
Sindwani T. Pelargonium sidoides for treatment of acute bronchitis. Altern Med Alert 2007;10(4):43-45.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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