By Donald J. Brown, ND
Although antibiotics continue to be used for the treatment of acute bronchitis and tonsillopharyngitis, there is a growing consensus among medical professionals worldwide that symptomatic treatment without antibiotics may be the preferred course of therapy in both conditions. With the exception of acute tonsillopharyngitis due to group A beta-hemolytic streptococcus (GABHS), recent clinical guidelines recommend that patients with GABHS-negative tonsillopharyngitis be told about the self-limiting nature of the illness and treated with supportive care only.1,2 Although predominantly caused by viral infections, some reports have placed the use of antibiotics for treatment of acute bronchitis as high as 70%.3 Overuse of antibiotics may lead to gastrointestinal disorders, allergic reactions, and the development of resistant organisms.
Although many traditional herbal remedies have been proposed for acute bronchitis and tonsillopharyngitis, few clinical trials have been performed to support their efficacy. One exception is the development of an extract of pelargonium (Pelargonium sidoides DC, Geraniaceae) roots, referred to as EPsâ 7630 (Umckaloaboâ). In recent years, the ethanolic root extract (1:9-11) has become a popular herbal medicine in Germany, approved for the treatment of acute bronchitis and acute tonsillopharyngitis, as well as acute sinusitis. New clinical trials (pending publication) also support its efficacy for the treatment of the common cold.
Botany and Traditional Use
A member of the Geraniaceae family, Pelargonium sidoides is native to the coastal regions of South Africa.4 Along with the closely related P. reniforme Curt, the root has been used for centuries in South Africa to treat coughs, upper respiratory tract irritations, tuberculosis, and gastrointestinal complaints.5 The Zulu used the terms "umKhulkane" (denoting respiratory infection) and "uHlabo" (roughly meaning chest pain) to describe what symptoms the root was used to treat. The herbal remedy was introduced to Europeans in the late 19th century by the Englishman Charles Stevens. On a trip to South Africa to seek a cure for tuberculosis, he consulted a tribal healer who gave him a strong decoction of the root of P. sidoides. Fully recovered, he returned to England with this new remedy and popularized it throughout Europe as "Stevens’ Consumption Cure."
The primary constituents of the root of P. sidoides include coumarins, tannins of the proanthocyanidin type, and simple phenolic compounds.6 Although the mechanism of action of the root extract is somewhat unclear, in vitro studies suggest that it may be related to antimicrobial7 and immunomodulatory8,9 properties that have been demonstrated for the tannins (e.g., catechin, gallocatechin, and gallic acid) and coumarins (e.g., umckalin). The immunomodulatory actions are mediated by the release of tumor necrosis factor alpha and nitric oxide as well as the stimulation of interferon release and an increase in natural killer cells.10
The subject of nine randomized trials conducted on a total of 1,477 patients (680 of them children ages 6-12 years) to date, EPs 7630 has been shown to safely and effectively shorten the severity and duration of acute bronchitis, tonsillopharyngitis, and sinusitis.6 Perhaps most notable has been the rapid recovery noted for children with GABHS-negative tonsillopharyngitis. On a practical note, the product used in these trials is palatable and easy to deliver to young children. Reports on two published trials follow.
Acute Non-GABHS Tonsillopharyngitis
In a randomized, double-blind, placebo-controlled trial, 143 children ages 6-10, with non-GABHS tonsillopharyngitis, received P. sidoides root extract (EPs 7630) or placebo at a dose of 20 drops (1 mL) three times per day for six days.11 Children were diagnosed less than 48 hours prior to starting the trial with a negative rapid test for GABHS and a Tonsillopharyngitis Severity Score (TSS) ³ 8 points. In the case of fever (³ 38.5° C), acetaminophen suppositories (500 mg) were allowed from day 0 to day 4. The main outcome measure was change in TSS from baseline (day 0) to day 4. TSS measures two subjective features of acute tonsillopharyngitis: sore throat and functional impairment (difficulty swallowing). It also objectively measures symptoms of inflammation: pharyngeal erythema and fever. Each symptom was assessed by an investigator using a 4-point rating scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe). Secondary outcome criteria included: 1) response criteria based on the TSS; 2) change of individual symptoms and further complaints including headache; 3) treatment outcomes according to the Integrative Medicine Outcome Scale (IMOS; complete recovery, major improvement, slight to moderate improvement, no change, deterioration); and 4) patient activity level. Following enrollment (day 0), controlled examinations occurred on days 2, 4, and 6. At each visit the investigator recorded clinical status, reviewed the patient’s diary, documented acetaminophen consumption, and recorded information about adverse events.
There was a statistically significant decrease in the primary outcome criteria (change in TSS from day 0 to day 4) in the EPs 7630 group compared with the placebo group. The decrease of TSS from baseline (day 0) to day 4 was 7.0 ± 2.4 points in the EPs 7630 group and 2.9 ± 2.4 points in the placebo group (P < 0.0001). On day 2, TSS decreased from 10.3 ± 1.2 to 6.8 ± 2.2 in the EPs 7630 group compared to 9.7 ± 1.4 to 8.2 ± 2.8 in the placebo group (P < 0.0001), suggesting an early response in the EPS 7630 group.
A TSS of < 5 points on day 4 was seen in 76.7% of patients in the EPs 7630 group compared with 34.3% of subjects in the placebo group (P < 0.0001). A decrease of at least 5 points by day 4 was seen in 91.8% in the EPs 7630 group compared with 35.7% in the placebo group. Rapid recovery, defined as fulfillment of secondary response criteria 1 and 2, was observed in 75.3% in the EPs 7630 group and 32.9% in the placebo group (P < 0.0001). There also was an improvement seen in the activity level of subjects in the EPs 7630 group, but not in the placebo group. By day 6, the number of patients returning to school was 80.8% in the EPs 7630 group compared with 21.4% in the placebo group (P < 0.0001). Subjects in the EPs 7630 group consumed less acetaminophen than did subjects in the placebo group. No serious adverse events were reported.
To determine the efficacy of EPs 7630 for treating acute bronchitis, 468 adult male and female subjects (age > 18 years) diagnosed with acute bronchitis for < 48 hours and having a Bronchitis Severity Score (BSS) > 5 points were recruited for a randomized, double-blind, placebo-controlled trial.12 Patients received either EPs 7630 or placebo at a dose of 30 drops (1.5 mL) three times per day for seven days. In the case of fever (> 39° C), acetaminophen tablets (500 mg) were allowed.
The primary outcome measure was change in the BSS on day 7 compared to the baseline score. BSS measures the following features of acute bronchitis: cough, sputum, rales/rhonchi, chest pain during coughing, and dyspnea. Each symptom was scored by an investigator using a 5-point rating scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe). Secondary outcome measures included: 1) prospective defined response criteria based on the BSS (A: BSS < 3 points; B: decrease of BSS ³ 7 points; C: A+B); 2) treatment outcome according to IMOS; 3) onset of treatment effect; 4) consumption of acetaminophen; 5) change of individual symptoms of BSS and further symptoms; 6) patients’ health status using health-related quality-of-life questionnaires (SF-12 Health Survey, EQ-5D); and 7) questions about the complaints and satisfaction with treatment using the Integrative Medicine Patient Satisfaction Scale (IMPSS). Following enrollment (day 0), controlled examinations occurred on day 3, 4, or 5, and on day 7. At each visit the investigator recorded clinical status, reviewed the patient’s diary, documented the consumption of acetaminophen, and recorded the number of adverse events. On day 7 there was a final assessment, which included laboratory tests and sputum analysis.
On day 7, BSS had decreased by 5.9 ± 2.9 in the EPs 7630 group and by 3.2 ± 4.1 in the placebo group compared to baseline. The 95% confidence interval for the difference of effects between the two treatment groups (EPs 7630 minus placebo) was calculated as -3.359 to -2.060, showing a significant superiority of EPs 7630 over the placebo by day 7 (P < 0.0001). This statistically significant difference was observed as early as the first follow-up visit (day 3, 4, and 5) with a BSS score of 4.8 ± 2.3 points in the EPs 7630 group compared with 6.2 ± 3.0 in the placebo group (P < 0.0001). In patients with the highest BSS at baseline (BSS ³ 8 points), there was a statistically significant greater decrease in the BSS in the EPs 7630 group (6.8 ± 2.7) compared with the placebo group (4.5 ± 4.2) at day 7 (P < 0.0001). A BSS of < 3 points (response criteria A) was observed in 64% of patients in the EPs 7630 group compared with 37.9% in the placebo group (P < 0.0001). A decrease in BSS of at least 7 points (response criteria B) was observed in 43.3% of patients in the EPs 7630 group compared with 23.0% of patients treated with the placebo at day 7 (P < 0.0001).
Rapid recovery (defined as response criteria C) was observed in 34.3% of EPs 7630 patients compared with 20.4% receiving the placebo (P < 0.0001). There was a statistically significant improvement in the individual symptoms of rales/rhonchi and chest pain during coughing in the EPs 7630 group compared with the placebo group (P < 0.0001). In the EPs 7630 group, cough disappeared or improved in 89.2% of patients compared with 56.6% of patients in the placebo group (P < 0.0001), and sputum disappeared or improved in 66% of patients compared with 47.7% of those in the placebo group (P < 0.0002). On day 7, fever had disappeared in 96.9% of patients in the EPs 7630 group compared with 58.4% of those in the placebo group (P < 0.0001). Patients in the EPs 7630 group were able to return to work nearly two days earlier than the placebo-treated group (P < 0.0001). Adverse events were mild and similar in both groups: 8.6% in the EPs 7630 group and 6.8% in the placebo group. These events included ear-nose-throat and respiratory complaints, as well as mild gastrointestinal upset.
Dosage and Formulation
To date, acute bronchitis and acute non-GABHS tonsillopharyngitis have been the primary conditions studied in controlled clinical trials. The recommended dose of EPs 7630 for adults and children older than age 12 is 30 drops (1.5 mL) three times per day for seven days. Children ages 6-12 may take 20 drops (1.0 mL) three times per day. Unpublished observational studies have suggested that children younger than age 6 may take 0.5 mL three times per day.6 An alcohol-free form of the product is available and recommended for pediatric use. Efficacy, dosage, and duration of treatment for persons suffering from acute maxillary sinusitis as well as the common cold should become clearer with the publication of results of recently completed clinical trials.
Adverse Effects, Contraindications, and Drug Interactions
Controlled clinical trials such as the two reviewed above demonstrate that EPs 7630 is well-tolerated and safe for the short-term treatment of acute bronchitis and tonsillopharyngitis. Open-label, observational studies with more than 2,500 adults and children suffering from acute bronchitis, acute tonsillopharyngitis, or acute maxillary sinusitis have found adverse events occurring in 1.2-15.5% of subjects.6 In only 1.6% of these cases was there a probable or possible connection made to EPs 7630. Adverse events have been largely mild, consisting of gastrointestinal complaints and skin rash.
The extract of P. sidoides root is contraindicated during pregnancy and lactation as no specific data on pregnant or lactating women are available. To date, there are no other contraindications or known drug interactions with the root extract.
P. sidoides root (EPs 7630) is a safe and effective treatment option for acute bronchitis and acute non-GABHS tonsillopharyngitis. Clinical studies suggest that it limits both the severity and duration of these respiratory tract infections. This botanical remedy offers health care professionals an alternative to antibiotics for the acute treatment of these conditions. Future clinical trials may also determine whether P. sidoides can be used concomitantly with antibiotics to provide added symptom relief.
Clinicians can employ a specific extract of P. sidoides, EPs 7630, for acute treatment of uncomplicated acute bronchitis and non-GABHS tonsillopharyngitis. Such treatment can be recommended for adults and children alike, but administration should be limited to no more than seven days. Extracts of P. sidoides should not administered to women who are pregnant or breastfeeding, nor to children younger than age 6, pending further research. [Editor’s note: Portions of this text were taken with permission from the author’s review of Pelargonium sidoides published in the peer-reviewed journal HerbalGram.]
Dr. Brown is the founder and director of Natural Product Research Consultants, Inc. He serves on the Advisory Board of the American Botanical Council and the President’s Advisory Board of Bastyr University. Dr. Brown has served as an advisor to the Office of Dietary Supplements at the National Institutes of Health.
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