Application of Enterosorption Method with Organosilicon Enterosorbent Enterosgel in the Integrated Treatment of Allergic Diseases

J. Bystron

Department of Allergology and Clinical Immunology, University Hospital Olomouc, Czech Republic, 2009

Abstract

This pilot, randomized, controlled study was carried out for evaluation of the safety and efficacy of Enterosgel application, concomitantly with standard therapy of patients with skin allergies (atopic dermatitis and chronic urticaria) and respiratory allergic diseases (atopic asthma and allergic rhinitis) in the exacerbation stage. Effect of Enterosgel was assessed in 24 patients during 21 days of treatment. A control group was composed of the same patients before the Enterosgel application. Combination therapy with Enterosgel has shown to have a very good effect: statistically significant improvement for bronchial asthma, chronic urticaria and other examined immune pathological conditions (polyvalent and food allergy, chronic fatigue syndrome).

Keywords: adsorbent, allergic diseases, atopic dermatitis, asthma, enterosorbent, Enterosgel, urticaria

Introduction

The Gastrointestinal (GI) tract plays an essential role in pathogenesis of allergic diseases. Decreased enzyme activity, disruption of intestinal motility, improper digestion and malabsorption lead to increased intestinal permeability to toxic compounds and macromolecules, which can lead to sensitization of the immune system. For this reason as part of a comprehensive treatment of various allergic diseases, it is highly desirable to protect the GI tract and normalize the intestinal microflora. These requirements are met by Enterosgel – an innovative intestinal adsorbent with a high sorption capacity and a protective effect on the intestinal mucous membrane and a positive influence on the intestinal microflora [1, 2]. The main objective of this study was to evaluate the safety and clinical efficacy of intestinal adsorbent Enterosgel in patients suffering from allergic diseases.

Materials and methods

This study involved 24 patients (10 men and 14 women aged from 2 to 80 years, average age is 43,1) diagnosed with: mild to moderate stable bronchial asthma (6 patients), chronic urticaria (7 patients), stable atopic dermatitis (6 patients) and 5 patients with a different diagnosis (1 patient with polyvalent allergy and indigestion, 1 patient with food allergy, 2 patients with chronic fatigue syndrome and 1 patient suffering from chronic uveitis, chronic keratitis and recurrent stomatitis). The patients arrived at the allergological outpatient department due to deterioration of their disorders or in relation to the regular control over their medical condition. A point-based assessment was carried out during 21 days prior to the commencement of Enterosgel application (control group), and further during 21 days of regular taking of Enterosgel (experimental group). Patients were randomized to groups according inclusion and exclusion criteria.

Basic inclusion criteria:

  1. Patients over 2 years with an allergic disease (see above patient samples).
  2. Patients with the prerequisite to cooperate properly in the course of study, who gave a written informed consent to participate in the study.

Basic exclusion criteria:

  1. Hypersensitivity to the medical product Enterosgel in their medical anamnesis.
  2. Patients from whom proper cooperation cannot be expected.
  3. Absence of a written consent to participate in the study.
  4. Participation in any other research within the previous 3 months.
  5. Patients treated with enterosorbents, probiotics and prebiotics within the last 30 days.

After signing the written informed consent, patients were given a Patient’s Diary to record their point-based assessments of disorders, according to their individual diseases.

Dosage of Enterosgel

For adults and children over 6 years of age: 1 tablespoon (15 g) 3 times a day (45 g/ day) stirred in a glass of water, taken 2 hours after meals or 1–2 hours before meals. An adequate water intake was recommended over the course of Enterosgel application, i.e. not less than 1.5–2 litres of liquids per day.

For children under 6 years of age: 1 teaspoon (5 g) 3 times a day (15 g/day) in the same regimen as above. Daily intake of liquids should not be less than 0.5 litres.

The following medicines and products were forbidden for use over the course of the study:

any enterosorbents, prebiotics and probiotics.

The following drugs were allowed to be used:

all drugs previously taken by the patients as well as such drugs which are officially accepted by modern standards for treatment of the specified diseases.

Point-based symptom assessment

The patient’s symptom severity was assessed by the point-based symptom score regarding individual diseases:

  • 1 point – significant deterioration;
  • 2 points – deterioration;
  • 3 points – current condition;
  • 4 points – improvement;
  • 5 points – significant improvement.

The clinical parameters which were monitored for the individual diseases:

  • bronchial asthma (8 items): general wellbeing, dyspnea, wheezing, difficulty in breathing (chest tightness), cough, nocturnal dyspnea, quality of sleep, everyday activities;
  • atopic dermatitis (9 items): general wellbeing, erythema (redness), new lesions, weeping, scratching / excoriations, xerosis (dryness of skin), itching, quality of sleep, everyday activities;
  • chronic urticaria (8 items): general wellbeing, new lesions, mean wheal diameter, itching, scratching, facial edema, quality of sleep, everyday activities;
  • other diseases (8 items): general well-being, headache, abdominal pain, joint pain, muscle pain, regularity of bowel movements, quality of sleep, everyday activities.

The initial value was equal to 3 points that correspond to the symptoms as of the monitoring commencement date. During the following days, the patients assessed their symptoms in the range of 1–5 points.

The 21-day period prior to the application of Enterosgel was used as a control. The 21-day period of Enterosgel use was used as experimental.

Laboratory and functional tests

Laboratory investigations were performed for all patients on following dates:

  • first examination (day 0);
  • second examination (day 21) prior to the commencement of Enterosgel treatment;
  • third examination (day 42) that is integrally 21 days after start of the Enterosgel treatment.

The following tests were performed:

  • total serum IgE levels and specific IgE, especially as a response to the causative allergens (according to the medical anamnesis or to previous skin prick tests);
  • blood chemistry tests: urea, creatinine, bilirubin, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and amylase (AMS).

A Spirometria was performed on patients with bronchial asthma.

Statistical estimation

Statistical analysis was performed at the Department of Medical Biophysics Faculty of Medicine and Dentistry Palacký University (Mgr. Langrová). The comparison of outcomes before and after Enterosgel application, was used for each and every patient. The paired Student’s t-test, Wilcoxon signed-rank test and linear regression analysis were used for statistical calculations. The paired samples t-test was applied when sample data was normally distributed. If the sample data was not normally distributed we used Wilcoxon test.

Results and discussion

Assessment of symptoms in the patients with bronchial asthma

Table 1 shows the values of the pointbased assessment of symptoms by individual patients, within the period before the commencement of Enterosgel application, as well as during the subsequent 21-day period of its application. With respect to the initial point-based value, the current status makes 24 points.

Table 1.

Symptom scores of individual patients with bronchial asthma during the control and experimental periods (from day 0 to day 21)

Control group (n = 6)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24222222232324242424242222202020212120192424
24242424242222222020202021212123232424242424
24242424242424242424202020202324242424242424
24242424242424242424242424242424242424242424
24191919292929292929191929292424242424242424
24253029242124222519242423231621182524172418
Experimental group (n = 6)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24242528282831313230303232303030262630303030
24242422242424252526252529302523252525272627
24242627252628252524201920202525272727272828
24242424252525252626262626272727272727272727
24292929191919292929291921292929232929222224
24232529242424252423172424222424242424242423

The average values of the point-based assessment of symptoms for individual days of monitoring is shown in the Figure 1.

Figure 1.

Enterosgel application: influence on the symptom score in the patients with bronchial asthma (n = 6; p = 0.024)

Enterosgel application: influence on the symptom score in the patients with bronchial asthma (n = 6; p = 0.024)

Assessment of symptoms in patients with atopic dermatitis

Below are the values of the point-based assessment of symptoms by patients during the period before Enterosgel application, as well as during the subsequent 21-day period of its application (Table 2). With respect to the initial point-based value, the current status makes 27 points.

Table 2.

Symptom scores of individual patients with atopic dermatitis during the control and experimental periods (from day 0 to day 21)

Control group (n = 6)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
27272724242727272727272727272727272727272727
27242723252326272728252526272727272727272727
27171722202124222223262625252616202227181818
27212021212223242022212322212424262727272727
27272328283030221915152926252019272727271920
27272724252727272726262727272727272727272727
Experimental group (n = 6)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
27383838373333333230353433323230282725222121
27242223232528312928282826272831262427222232
27261212141619141718161616192122252324232324
27272727212121212127272726262521212118181821
27272121283022222621192024261832183227282121
272726

The average values of the point-based assessment of symptoms for individual days of monitoring is shown in the Figure 2.

Figure 2.

Enterosgel application: influence on the symptom score in the patients with atopic dermatitis (n = 6; p = 0.049)

Enterosgel application: influence on the symptom score in the patients with atopic dermatitis (n = 6; p = 0.049)

Assessment of symptoms in patients with chronic urticaria

Table 3 shows the values of the pointbased assessment of symptoms by individual patients during the period before the commencement of Enterosgel application, as well as during the subsequent 21-day period of its application. With respect to the initial point-based value, the current status makes 24 points.

Table 3.

Symptom scores of individual patients with chronic urticaria during the control and experimental periods (from day 0 to day 21)

Control group (n = 7)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24242424242424252522222220202024242424242424
24242424242424242424242424242424242424242424
24242424242424242424242424242424242424242424
24242424242424242222222222222424242420202024
24242424242424242424242424242424242424242424
24242225242424242223232423232323232324242424
24242424242424242424242424242424242424242424
Experimental group (n = 7)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24242424242424242426262624262627272626282828
24222220202022222020202022222322232223232221
24242224221819242424241820252524242119252523
24232323222323242322222424262726293028282829
24261821232327303030303028293030313131313131
24232323202020232323232323232322222323232324
24253024253736373737373737382227303636253132

The average values of the point-based assessment of symptoms for individual days of monitoring is shown in the Figure 3.

Figure 3.

Enterosgel application: influence on the symptom score in the patients with chronic urticaria (n = 7; p = 0.027)

Enterosgel application: influence on the symptom score in the patients with chronic urticaria (n = 7; p = 0.027)

Assessment of symptoms in patients with other diseases

Table 4 shows the values of the pointbased assessment of symptoms by individual patients, during the period before the commencement of Enterosgel application, as well as during the subsequent 21-day period of its application. With respect to the initial point-based value, the current status makes 24 points.

Table 4.

Symptom scores of individual patients with other diseases during the control and experimental periods (from day 0 to day 21)

Control group (n = 5)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24242420191921212426303030292724242424242424
24181919191718161720201816202018201820202120
24182424222022212420192322202020211818222324
24242424242424242424242424242424242424242424
24242424242424242424242424242424242424242424
Experimental group (n = 5)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
24242831312725262424242427282828283131313333
24242222222222202024282828282728232320242424
24242426283030282826292524181920242422262624
24242424283030302828282828282828282828282828
24262727303232323232323234343434343434343434

The average values of the point-based assessment of symptoms for individual days of monitoring is shown in the Figure 4.

Figure 4.

Enterosgel application: influence on the symptom score in the patients with other diseases (n = 5; p = 0.004)

Enterosgel application: influence on the symptom score in the patients with other diseases (n = 5; p = 0.004)

Subjective evaluation of the therapeutic effect on the part of the patients

After the application of Enterosgel came to an end, the patients were provided with a questionnaire regarding their general impression of taking the medical product. It contained questions on whether the application had deteriorated the basic disease, whether the condition was left unchanged, whether there was any improvement in the basic manifestations of the main disease, and whether there was a significant improvement in health condition. Furthermore the patients stated their subjective feelings, which they were most strongly aware of over the course of treatment.

There was only 1 patient who demonstrated a refusal to take Enterosgel, which also persisted after the dosage and taste of the drug had been changed, and therefore the treatment was stopped. 5 patients did not report any changes in their health condition. 17 patients (74%) evaluated the Enterosgel treatment as beneficial (Figure 5).

Figure 5.

Subjective evaluation of effects of Enterosgel by patients (n = 23)

Subjective evaluation of effects of Enterosgel by patients (n = 23)

Observed improvement in health apart from the basic disease:

  • improvement of digestion, relieving symptoms of indigestion, normalization of stool – 35%;
  • improvement in the itching condition – 17%;
  • alleviation or reduction of fatigue – 13%;
  • improvement in sleep quality – 13%;
  • improvement in breathing – 4%;
  • relieving symptoms of allergic rhinitis – 4%;
  • reduction symptoms of food allergies – 4%;
  • improvement in atopic dermatitis – 4%.

Deterioration or adverse events:

  • vomiting, in 1 patient the Enterosgel treatment was stopped prematurely after 3 days of application (no improvement after reduction of dosage and change of the taste);
  • sensation of abdominal bloating in 1 patient;
  • occasional myalgia and arthralgia in 1 patient.

Data of laboratory and functional tests

A statistical analysis of the laboratory data did not show any statistically significant changes in the test results. Neither were statistically significant changes recorded in the spirometric values of the patients with bronchial asthma.

The absence of statistically significant changes in the monitored parameters can be explained by the fact that basic biochemical values in all the patients were within with the reference values. As regarding the values of total and specific IgE, the 21-day duration of treatment is evidently too short a period to reflect (to influence them) the dynamics of their changes.

Conclusions

This study provides evidence of the superiority of combination therapy with adsorbent Enterosgel in the treatment of allergic diseases. It was determined that:

  1. Enterosgel has demonstrated safety and high tolerability. The treatment was stopped prematurely after 3 days of taking in 1 patient only (due to nausea and vomiting). One 7-year-old girl did not like the taste of Enterosgel, but there were no reasons for suspending or stopping the treatment.
  2. No statistically significant influence on the patients with atopic dermatitis was determined.
  3. No statistically significant changes in the laboratory parameters (total and specific IgE, IgE, urea, creatinin, bilirubin, cholesterol, AST, ALT, and AMS) were recorded.
  4. 74% of the patients observed improvement of their health, apart from the basic disease, which was manifested as an improvement of digestion, relieving symptoms of indigestion, normalization of stool, improvement in the itching condition, alleviation or reduction of fatigue, improvement in sleep quality, improvement in breathing, relieving symptoms of allergic rhinitis, reduction of food allergy symptoms.
  5. Statistically significant improvement in the clinical scores, according to pointbased assessment, proves the clinical efficacy of Enterosgel, concomitantly with standard treatment in patients, with bronchial asthma, chronic urticaria and other examined immune pathological conditions (polyvalent and food allergy, chronic fatigue syndrome).

References

  1. Maev IV, Shevchenko YuN, Petukhov AB, editors. [Clinical application of Enterosgel in patients with gastrointestinal disturbances: novel approaches to treatment: Guidelines for physicians]. M.: 2000 (in Russian).
  2. Paliy IG, Reznichenko IG. [Modern view on the problem of enteral sorption: selection of optimal medication]. Liky Ukrainy. 2008;6(122):43– 46 (in Russian).