Treatment effect and safety of EPs[R] 7630-solution in acute bronchitis in childhood: report of a multicentre observational study.
An open post-marketing surveillance study was conducted to examine the treatment effect and safety of EPs[R] 7630-solution in the treatment of acute bronchitis in children.
This study included a total of 742 children (aged between 0 and 12 years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%), who were treated with different doses of the herbal drug for up to 14 days. Five bronchitis specific symptoms (BSS) were summed up to give an overall measure of disease severity. Nonspecific disease symptoms (loss of appetite, diarrhoea, headache, vomiting, and fever) were also recorded, together with adverse events and overall ratings of efficacy and tolerability.
The overall BSS score decreased during treatment from 6.0[+ or -]3.0 points at baseline to 2.7[+ or -]2.5 points after 7 days and to 1.4[+ or -]2.1 points after 14 days. Remission or improvement in at least 80% of patients was recorded for all the individual component symptoms. The proportion of patients suffering from non-specific symptoms also substantially improved during treatment. For example, loss of appetite was present in 65.8% of patients at study begin, but only in 27.6% at the time point of last observation visit. In 88.3% of cases, the responsible physician rated the treatment as successful. Adverse events were minor and transitory.
In conclusion, EPs[R] 7630-solution was shown to be a safe and an effective treatment option for acute bronchitis or acute exacerbations of chronic bronchitis in children.
[c] 2006 Elsevier GmbH. All rights reserved.
Keywords: Acute bronchitis; Children; Herbal medicine; Bronchitis severity score; EPs[R] 7630; Umckaloabo[R]
Acute bronchitis is one of the top ten conditions for which patients seek medical care (Knutson and Braun, 2002). The great majority of cases are due to viral infection, although bacterial infections and allergies may play a role. The pathogen is often not identified (Knutson and Braun, 2002; Flaherty et al., 2001; Gonzales and Sande, 2000).
Apart from rhinitis, acute bronchitis is the most commonly diagnosed disease in paediatric practices. An infection of the bronchi alone is rare, however, and usually tracheobronchitis is present, with involvement of other areas of the respiratory tract. The pathogens in children are predominantly RNA viruses, especially the respiratory syncytial virus, followed by Coxsackie, influenza, para-influenza and ECHO viruses, or adenoviruses as representatives of the DNA group.
Over the normal course of acute bronchitis, a child initially suffers from a dry unproductive cough, which starts gradually about 3-4 days after rhinitis. This is often accompanied by dull substernal pain or burning chest pain, exacerbated by coughing. As the illness advances, wheezing, a feeling of soreness in the chest and dyspnoea may sometimes occur. Coughing fits and viscous choking mucous can result in vomiting. Within a few days, the cough becomes productive and the expectorate has a purulent appearance. Over the next 5-10 days, the expectorate then becomes thinner and the coughing usually gradually decreases. The general feeling of ill-health can however continue for several days (Stern, 1987).
Laryngitis with hoarseness, headache and pain in the limbs are often concomitant symptoms of a viral infection. Young children, in particular, often have no appetite and no wish to play. In younger children, diarrhoea occurs occasionally.
The destabilised defence mechanisms resulting from a viral infection can clear the way for a secondary bacterial infection. One of the first indications can be the change in coughing to a productive stage, with purulent, but rarely bloody, expectorate. However, a thick, slightly purulent expectorate is also common in viral infections. The temperature is normally sub-febrile in viral infections, but can rise. However, only the associated changes in blood count and other inflammatory parameters provide definite confirmation. In 70% of cases, the bacterial pathogens involved are pneumococci and Haemophilus influenzae, but Moraxella catarrhalis, [beta]-haemolytic streptococci and Staphylococcus aureus may also be present (Bubenzer, 1993).
Without treatment, there is a risk of ENT involvement, such as otitis media or sinusitis and, particularly in infants, the danger of bronchiolitis or pneumonia. Depending on constitutional disposition and allergic reactivity, the inflammatory process may also become chronic. Although chronic bronchitis from exogenous causes is rare in children and presents no characteristic picture, frequent relapses without adequate recovery phases, exacerbated by environmental factors such as air pollution and tobacco smoking, can lead to similar clinical symptoms and can provide the basis for chronic development in adulthood, with irreparable damage to the bronchial mucosa in some cases (Reinhard, 1993; Schwartz, 2004).
Treatment of acute bronchitis is usually symptomatic, with tussives or antitussives (Knutson and Braun, 2002). Antibiotics are often prescribed, but cannot be generally recommended, unless the acute bronchitis presents as an exacerbation of chronic bronchitis or is clearly of bacterial origin (Gonzales et al., 2001; Ben-David and Rubinstein, 2002; Martinez, 2004; Edmonds, 2002). There is little evidence to support the use of [[beta].sub.2]-agonists (Smucny et al., 2004). In this context, a new approach to treatment would be of clinical interest.
EPs[R] 7630-solution (1) is a liquid herbal preparation from the roots of Pelargonium sidoides, used in traditional medicine in South Africa, and has been shown to have immunomodulatory properties, including stimulating interferon activity and increasing the number of natural killer cells (Kayser et al., 2001). The efficacy and safety of EPs[R] 7630-solution in acute bronchitis have already been demonstrated in clinical studies and outcomes studies with adult patients (Chuchalin et al., 2005; Matthys and Heger, 2006) or children (Blochin et al., 1999). The present article reports a post-marketing surveillance study on the use of EPs[R] 7630-solution in the treatment of acute bronchitis in children.
Materials and methods
The study was carried out between October 1993 and February 1995 at a total of 158 centres in Germany under the scientific management of the Ludwig Boltzmann-Institute for Homoeopathy, Graz, Austria.
The target population comprised children between 0 and 12 years of age with acute bronchitis or acute exacerbation of chronic bronchitis, possibly with concomitant infections, such as sinusitis, rhinitis, pharyngitis and tracheitis. The exclusion criteria included antibiotic treatment in the pre-phase or at the start of therapy. Patients with a history of liver disease or blood coagulation disorders were also excluded.
Children up to 2 years were given 3 x 5 drops EPs[R]-solution per day, children between 2- and 6-year old were given 3 x 10 drops/day and children over 6 years were given 3 x 20 drops/day. EPs[R]-solution contained 80g EPs[R] 7630 in 100ml solution and was to be taken with some liquid, before meals and over a maximal period of 2 weeks.
Subjective complaints, concomitant diseases, concomitant medication and non-medical measures were documented by the physician at the initial examination and after 7 and 14 days. A diary with details of dosages and subjective complaints was kept by the parents over the whole observation period.
The primary efficacy parameter was the change in the total score of five bronchitis specific symptoms (BSS)--cough, sputum, dyspnoea, rales/rhonchi, and chest pain during coughing--assessed by the physician by use of a five point verbal rating scale (from 0 for 'absent' to 4 for 'severe').
In addition, the non-specific symptoms 'lack of appetite', 'fever', 'vomiting', 'diarrhoea', and 'headache' were recorded, together with adverse events. The overall therapeutic success was rated by the patient or parent and the physician, using a five-point scale, ranging from 'remission' to 'deterioration'. Tolerability was rated by the patient or parent and the physician on a four-point scale, ranging from 'very good' to 'unsatisfactory'.
A total of 742 children (aged 4[+ or -]3 years; 337 girls, 388 boys, 17 no data) were enroled, with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%, with an average of four relapses per year) (2.3% no data). The age distribution was as follows: up to 2 years: 237 children (32%); between 2 and 6 years: 321 children (43%); older than 6 years: 168 children (23%). In 93.3% of the patients, multiple concomitant infections were reported, including rhinitis (79.2%), pharyngitis (44.5%), tracheitis (19.0%) and sinusitis (15.6%). The bronchitis had been present for 1-2 days in 35.4%, 2-7 days in 38.4% and for longer than 1 week in 24.8% of the cases.
In total, 384 patients (51.8%) took no further medication during the study. Concomitant medication for the other patients was predominantly antitussive agents and expectorants (26.5%), rhinilogical agents (12.8%) and broncholytic agents (6.5%). Supporting measures (mostly chest, throat and leg compresses or inhalations) were received by 44.5% of the children at baseline and by 17.7% in the second week.
The overall BSS score decreased during treatment from 6.0[+ or -]3.0 points at baseline to 2.7[+ or -]2.5 points after 1 week and to 1.4[+ or -]2.1 points at the end of the study. This corresponds to an average drop of 4.7 points (p<0.001; Wilcoxon test, two sided). According to the overall BSS score, complete or partial remission of bronchitis was achieved in 90.2% of children. Subgroup analysis showed a higher decrease in the overall BSS (5.4-6.1 points) in children with acute exacerbations of chronic bronchitis (including those with allergic bronchitis), or with concomitant sinusitis and tracheitis compared to the total population. Previous treatment with other therapeutic agents such as antitussive agents and antibiotics, but also concomitant medication with an effect on the respiratory tract, was more likely to have a negative effect on the therapeutic success (score reduction: 4.4-4.5 points). Supporting measures produced no additional therapeutic benefit. Separate analysis of the components of BSS found remission or improvement for more than 80% of all patients (Table 1).
The non-specific symptoms (loss of appetite, vomiting, diarrhoea, headache, fever; Fig. 1) also improved substantially. In particular, loss of appetite was present in 65.8% of patients before treatment, but only in 27.6% afterwards. Fever was present in 61.9% of patients before treatment, but only in 16.6% afterwards.
According to the information in the patient diaries, complete remission of the symptoms headache, pains in the limbs and sore throat occurred within 3 days on average and of cough within 8 days. An early onset of action was reported mainly in patients for whom therapy started within 48 h of the outbreak of bronchitis, as well as in children with acute exacerbations of chronic bronchitis. Complete or partial remission of the symptoms complex was found in 83.5% of cases within 1 week (Fig. 2).
In 88.3% of cases, the responsible physician rated the treatment with EPs[R] 7630-solution as successful, 58.2% of the children were free of symptoms and 30.1% had improved considerably or had recovered. In total, 85.2% of the patients confirmed the success of therapy: 56.3% reported that they were symptom-free and 28.9% reported a clear improvement or recovery.
Tolerability was rated as good or very good in 94.9% of cases (3.2% no data) (Fig. 3). During the course of the study, 13 adverse events (1.8%) were documented, the severity of which was almost always be described as mild to moderate. In 8 (1.1%) cases, a causal relationship to the test medication was not excluded. In 3 patients, an intensification of existing respiratory symptoms or clinical concomitant symptoms such as fever was reported; in 2 children, exanthema occurred; in 2 patients, psychomotor unrest with crying fits or dyspnoea was reported; in 1 patient, diarrhoea was reported. Usually, the adverse events disappeared within 2 days. In a total of 5 of these patients, the test medication was discontinued. A subsequent treatment with antibiotics was only considered necessary in two cases due to an increase in the respiratory complaints.
Inflammation of the bronchial mucosa occurs more often and is more severe in children than in adolescents or adults. This frequency increases dramatically during the cold and damp autumn and winter months and can hinder the development of the growing child. Furthermore, a continuously weakened endogenous defence system facilitates the development of chronic bronchitis and increases the risk of complications. Therapeutic steps in the initial phase of the disease are therefore decisive. In view of the predominantly viral aetiology, the treatment concept generally comprises symptomatic measures to minimise the duration of the illness and to prevent super infection. The administration of classic antibiotics is facing increasing criticism. Outside the strict indication for antibiotic treatment, there is therefore a need for an alternative therapeutic agent, which effectively reduces the respiratory symptoms, counteracts bacterial superinfection and is well tolerated.
The present article describes an open and uncontrolled study in which 742 children with acute bronchitis or acute exacerbations of chronic bronchitis were treated with EPs[R] 7630 for a mean period of 14 days. The mean reduction in BSS was reported as 4.7, with particularly favourable results in patients with allergic bronchitis or acute exacerbations of chronic bronchitis. Major improvements were also found in the non-specific symptoms (loss of appetite, vomiting, diarrhoea and fever) and in the component symptoms of the BSS score (cough, sputum, dyspnoea, rales/rhonchi and chest pain). Remarkably, coughing, the most intractable symptom in bronchitis, showed a clear improvement in 86.3% of cases, and in almost half of these patients to remission. In addition, only mild and temporary adverse events were reported and ratings of tolerability were very good.
These results are consistent with those of a smaller study reported by Dome and Schuster (1996). In their uncontrolled observational study in 259 children with acute bronchitis, the BSS fell from 6.0[+ or -]2.9 points to 2.3[+ or -]2.8 points within 2 weeks. Only a few mild- and short-term adverse events were recorded.
Although this was an uncontrolled post-marketing study, the findings indicate that EPs[R] 7630-solution is a safe treatment of acute bronchitis in children outside the strict indication for antibiotic treatment and represents a valuable addition to the therapeutic armamentarium.
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M. Haidvogl (a,*), M. Heger (b)
(a) Ludwig Boltzmann-Institute for Homoeopathy, Graz, Austria
(b) ISO-Pharmaceuticals, Ettlingen, Germany
[star]This study was originally published in Zeitschrift fur Phytotherapie 1996; 17(5):300-313.
*Corresponding author. Schillerstrasse 11. 8010 Graz, Austria.
E-mail address: Max.email@example.com (M. Haidvogl).
(1) EPs[R] 7630 is exclusively contained in Umckaloabo[R] (marketed by Spitzner Arzneimittel, Ettlingen, Germany).
Table 1. Effect of EPs[R] 7630 treatment on the individual symptoms of bronchitis at day 14 Remission Improvement Remission or Symptom (%) (%) improvement (%) Cough 45.9 40.7 86.6 Sputum 68.7 14.3 83.0 Dyspnoea 86.2 2.9 89.1 Rales/ 73.2 12.2 85.4 Rhonchi Chest pain 85.0 1.9 86.9 Given are per cent of patients with remission, improvement and remission or improvement, respectively, after a maximum of 14-day treatment with EPs[R] 7630 (n = 742). % Patients Initial Investigation Final Observation Loss of Appetite 65.8 27.6 Vomiting 16.3 5.9 Diarrhoea 4.6 2.8 Headache 31.7 7.5 Fever 61.9 16.6 Fig. 1. Percentage of patients with non-specific symptoms before and after a maximum of 14-day treatment with EPs[R] 7630 (n = 742). Note: Table made from bar graph. Percentage Physician Patient or parents Remission 58.2 56.3 Marked improvement 24.8 23.2 Improvement 5.3 5.7 Unchanged 3.9 3.9 Deteriorated 5.8 5.8 Not given 2 5.1 Fig. 2. Assessment of efficacy of EPs[R] 7630 by the physician and by the patient or parents after a maximum of 14-day treatment with EPs[R] 7630 (n = 742). Note: Table made from bar graph. Percentage Physician Patient or parents Very good 64.6 62.1 Good 30.3 29.6 Moderate 0.9 2.8 Unsatisfactory 0.9 0.8 Not given 3.2 4.6 Fig. 3. Assessment of tolerability of EPs[R] 7630 by the physician and by the patient or parents or parents after a maximum of 14-day treatment with EPs[R] 7630 (n = 742). Note: Table made from bar graph.
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|Author:||Haidvogl, M.; Heger, M.|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Article Type:||Clinical report|
|Date:||Feb 1, 2007|
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