A preventive measure for otitis media in children with upper respiratory tract infections

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Abstract

Recurrent upper respiratory tract infections (URTI) are very common in patients of all ages. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population. The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Eighty-four paediatric patients of both sexes (range: 4–14 years) with otitis were enrolled in the study. Patients were included if they had a >2 years' history of recurrent or chronic respiratory infections, and/or had experienced at least three episodes requiring medical consultations and/or treatment during the winter prior to the study. The young patients were randomised to receive Immucytal (group A) or placebo (group B) treatment according to the following protocol: (1) starting therapy (1 month): one tablet daily in the morning 4 days per week for 3 consecutive weeks; (2) maintenance period (5 months): one tablet daily in the morning 4 days per week for 1 week every month. Placebo and Immucytal tablets were identical in shape and size, in order to maintain double-blind conditions. Patients of group A with recurrent URTI had a significantly decreased incidence of ENT infections, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work-days lost. The reduction in the incidence of infectious episodes became significant vs. placebo. A significantly improved outcome vs. placebo was also observed on the incidence of fever, frequency and duration of infectious episodes, ancillary therapies. Immucytal treatment was associated with significant changes in both immunological and auditory function parameters. Serum concentrations of immunoglobulins were significantly increased in Immucytal. For both evaluations, a significant difference between treatment groups was found (P>0.001). Preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.

Introduction

Recurrent respiratory tract infections are very common in patients of all ages [1], [2], [3], [4]. Rhinitis, bronchitis, chronic sinusitis and otitis appear to be the prevalent forms of recurrent respiratory infections in the paediatric population [6], [8]. The first consequence of recurrent infections of the upper respiratory tract is the otitis media. Otitis media with effusion (OME) is an inflammatory condition characterized by the presence of secretion in the middle ear behind an intact tympanic membrane. OME may be classified according to its duration as acute (less than 3 weeks), subacute (between 3 weeks and 3 months), or chronic (more than 3 months).

OME is considered the most common disease of the childhood and there is no sex preponderance. About 80% of children are affected by OME at least once in their childhood and the highest incidence of this disease occurs between 5 and 7 years of age.

The aim of treatment is so the solution of the respiratory pathology and the also the prevention of their complications. A recent study indicates that the practice patterns of paediatricians, otolaryngologists and paediatric otolaryngologists differ from the recommendations of an evidence-based practice guideline [5]. Identification of the main bacteria causing OME in a given population is essential. It indicates the degree of involvement of a given bacterium in a particular disease of that population. Knowledge of the most prevalent bacteria would initiate the search for the mode of acquisition of such bacteria and may aid in establishing appropriate control and prevention programs, which may decrease the incidence of OME. The rapid response of most OME to a variety of broad-spectrum antimicrobials deprives the clinician from knowing the particular bacteriologic agent prevailing in a community. With the emergence of resistant strains and the change over time of the relative distribution of bacteriologic agents known to cause OME, the identification of the bacterial etiology of OME was initiated (43). Although viruses (Rhinovirus, Adenovirus, Virus respiratorio sinciziale, Influenza tipo A Virus, Parainfluena Virus) are usually the primary pathogens involved, superinfections with bacteria are frequent [9]. The most common bacteria involved in such infections are Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Moraxella (Branhamella) catarrhalis. Antibacterial therapy is still the classical treatment approach in patients both with respiratory tract infections and with otitis media, despite the fact that antibacterials have several well known drawbacks, especially when used to treat recurrent infections. Amongst other limitations, these drugs are not effective against viral infections, do not enhance the host's defence mechanisms against subsequent infections and, with prolonged use, may induce bacterial resistance. In contrast to antibacterials, ribosomal immunotherapy is designed to enhance both specific and non-specific immunity against the most common pathogens involved in respiratory tract infections. Many studies have demonstrated the immunostimulant activity of various bacterial extracts [10], [11], [12], which seems to target not only the bacteria from which such extracts are made, but also (trough non-specific mechanism) other pathogens responsible for the most common respiratory tract infections. This activity is essentially due to the non-specific adjuvant properties of bacterial ribosomes wall lipopoysaccharides and other cellular fractions that can be obtained by bacterial lysis [13], [14]. Moreover, these components are able to induce the production of secretory of IgA antibodies, which have several well-known properties related to specific and non-specific defence mechanism towards viruses and bacteria. IgA also prevent microorganisms from adhering to the epitelial surface and can prevent, therefore, subsequent colonisation [15], [16], [17], [18], [19], [20]. Immucytal is composed of ribosomal extracts from four bacteria: Klebsiella pneumoniae, Diplococcus pneumoniae, S. pyogenes and H. influenzae, in addition to membrane proteoglycans from Klebsiella pneumoniae. This agent was found to stimulate the activity of macrophages, polymorphonuclear cells and natural killer (NK) cells in leukocytes isolated from human peripheral blood [21], [22], [23], [24], and to modulate polymorphonuclear leukocyte (PMN) functions when administered alone or in associations with antibacterials [25], [26]. There is also evidence that Immucytal enhances specific immunity in adults and children, including antibody production [27]. In fact there is a presence of a link between allergic diseases and infectious diseases, which may have some important clinical implications. In a study with the children ranged from 10 to 18 years old (14.12±0.89 years), the prevalence of infectious disease was significantly higher in children with allergic disease symptoms (defined as asthma, allergic rhinitis or atopic dermatitis) [7]. The aim of the present study was to compare the efficacy and safety of an oral formulation of Immucytal vs. placebo in the prevention of otitis media in adult patients with recurrent upper respiratory tract infections (URTI). We evaluated the effects of Immucytal on clinical outcome as well as immunological, respiratory and auditory function parameters.

Section snippets

Materials and methods

This study was performed in Italy during the period from September to May 1999.

We had considered as exclusion criteria: congenital immunodeficiences (e.g. agammaglobulinemia, congenital lack of secretory IgA), ear, nose or throat (ENT) conditions secondary to gastroesophageal reflux or tooth infection, treatments with immunostimulant or immunosuppressive agents (i.e. levamisole, bacterial vaccines or corticosteroids) in the past 6 months, and a diagnosis of bronchopulmonary disease (i.e.

Results

Among the 84 enrolled patients, three did not complete the study (one in the Immucytal group and two in the placebo group). Two of these patients (one in each group) withdrew because of treatment-related reasons. The groups were homogeneous for demographic characteristics, weight, height, diagnosis and risk factors. The mean duration of treatment was 176 (range 89–236) days.

During the observation period, there was an overall clinical improvement, which was more evident in patients treated with

Discussion

The current management of otitis is based on curative measures, mainly antibacterials and symptomatic therapies. These treatments do not prevent the recurrence of infections: hence the high prevalence of these diseases and their relevant impact on healthcare resource utilisation. In this context, preventive strategies, such as ribosomal immunotherapy, may represent a valid alternative approach.

In this study of 6 months' duration, 84 patients (mean age 5.2 years) with otitis were randomised to

Conclusions

Treatment with Immucytal, administered orally for 6 months in paediatric patients with recurrent URTI resulted in a significantly decreased incidence of OME, fever and shorter duration of illness, decreased requirement for ancillary medications and fewer work or school-days lost.

Immucytal thus appears to be a very useful treatment approach in the prevention of otitis.

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