Role of immunoactivation with pidotimod in recurrent respiratory infections in childhood. Pidotimod in the treatment of recurrent respiratory infections in paediatric patients. Ribosomal immunostimulation: assessment of studies evaluating its clinical relevance in the prevention of upper and lower respiratory tract infections in children and adults. Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections. Isoprinosine does not protect against frequent respiratory tract infections in childhood. Levamisole (R 12564) in the prevention of recurrent upper respiratory tract infections in children: a double-blind, placebo-controlled study. Efficacy and safety of pidotimod in the treatment of recurrent respiratory infections in children. Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months. Use of a polyvalent bacterial lysate in patients with recurrent respiratory tract infections: results of a prospective, placebo-controlled, randomized, double-blind study. Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial. [Efficacy of sublingual polyvalent bacterial vaccine (Lantigen B) in children with recurrent respiratory infection: a randomized double-blind controlled clinical trial]. [Klebsiella pneumoniae glycoproteins as coadjuvants in the prevention of recurrent respiratory infections in children 1-6 years of age]. Ribosomal therapy in the prophylaxis of recurrent pharyngotonsillitis in children. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study. Clinical and immunobiological effects of an orally administered bacterial extract. A double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections. Broncho-Vaxom in children with rhinosinusitis: a double-blind clinical trial. Levamisole in prevention of recurrent upper-respiratory-tract infections in children. Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group. Immunoactivity of pidotimod against episodes of recurrent tonsillitis in childhood. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. [Treatment using immucytal in children with recurrent respiratory infections: an Italian multicenter experience]. Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial. Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels. [Effect of long-acting garlic tablets "allicor" on the incidence of acute respiratory viral infections in children]. Bacterial lysate (I.R.S. 19) applied intranasally in the prevention of acute respiratory diseases in children: a randomized double-blind study. [Biostim prevention of recurrent respiratory infections in children. A double-blind versus placebo study]. A placebo controlled, double-blind evaluation of levamisole in the reduction of the frequency, duration and severity of attacks in children suffering from recurrent upper respiratory tract infections. Pidotimod in the management of recurrent pharyngotonsillar infections in childhood. Short ribosomal prophylaxis in the prevention of clinical recurrences of chronic otitis media in children. Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study. Immunoactivation by pidotimod in children with recurrent respiratory infections. Ribosomal therapy in the treatment of recurrent acute adenoiditis. [Prospective placebo-controlled double-blind study using a bacterial lysate in infections of the respiratory tract and ENT region in children]. Efficacy of Lantigen B in the prevention of bacterial respiratory infections. [Clinical study concerning the prevention of infections of the upper respiratory tract of preschool children]. Reduction of the number and severity of respiratory tract infections in children by oral immunostimulation. A preventive measure for otitis media in children with upper respiratory tract infections. A double-blind pediatric evaluation of levamisole in the prevention of recurrent upper respiratory tract infections. [Prophylactic efficacy of reaferon in viral hepatitis A and acute respiratory infections in children]. [Evaluation of the effectiveness of thymomodulin in children with recurrent respiratory infections]. [Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of subacute sinusitis and the prevention of recurrent infections in children].
The efficacy and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) were rated in a child population with a remote history of recurrent respiratory infections (RRI). This randomized double-blind multicenter clinical trial versus placebo, stratified by age groups, involved 748 children recruited in 69 Medical Centres. The trial consisted of a 60-day treatment period and a 90-day follow-up. At the end of the treatment period the pidotimod group showed a significant decrease in the number of RRI episodes and associated symptoms vs control group. As a consequence, there was a significant decrease in the number of days of absence from kindergarten or school and in the consumption of antibiotics and symptomatic drugs. Safety was good. The effect of the drug persisted after its withdrawal throughout the whole 90-day follow-up period. During this period there was a significantly lower RRI incidence rate in the pidotimod group than in the placebo group (p < 0.01). Because of its efficacy and safety, pidotimod may be rated as an excellent drug in the RRI management in children. 50 young patients suffering from recurrent respiratory infections (RRI) were treated with pidotimod ((R)-3-[(S)-(5-oxo-2- pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) (one 400 mg ampoule twice a day) or placebo, according to a double-blind experimental design. The treatment period was 20 days and there was then a 60-day follow-up period. Evaluation was both clinical (number and severity of the respiratory infectious episodes) and immunological, investigating the OKT 4 and OKT 8 lymphocyte sub-populations and OKT 4/OKT 8 ratio. The group of children treated with pidotimod showed a decrease in the number of infections. Patients free from RRI episodes, after 20 days of therapy, were 68% of the group treated with pidotimod compared with 8% of the placebo group. In addition, the mean duration of the episodes was lower in treated patients than in patients of the control group. Such differences were statistically significant. It was also observed that administration of the drug potentiated the immune response such that the clinical picture remained improved for a further 60 days after treatment cessation. Furthermore, only in the pidotimod group there were improving changes of OKT 4 and OKT 8 percentages which affected the OKT 4/OKT 8 ratio. To review the efficacy of the ribosomal immunostimulant Ribomunyl in preventing upper and lower respiratory tract infections.
                Review of studies of 3 and 6 months' duration comprising part of the international registration file.
                Data from 2117 patients (1215 children and 902 adults); ribosomal immunostimulant n = 1062, placebo n = 1055.
                Nineteen randomised, double-blind, placebo-controlled clinical trials were performed between 1983 and 1994 in Europe. In children with ear-nose-throat (ENT) infections, 3 months' ribosomal immunostimulant treatment significantly decreased the mean number of recurrences (27-68% reduction), and reduced the duration of infection (28-66% reduction) and antibacterial requirement (29-60% reduction). Ribosomal immunostimulant was similarly effective in children with ENT and bronchopulmonary infections, reducing the mean number of recurrences by 32-61% compared with placebo. In children with otitis media, ribosomal immunostimulant reduced recurrences by 10-53% and also reduced the duration of infection, antibacterial use and local surgery requirement. Results obtained from studies of 6 months' duration confirmed or extended these results. In adult patients with ENT or mixed respiratory infections, ribosomal immunostimulant produced similar reductions to those seen in children for recurrent infections (54-78% reduction), duration of infection (42-79% reduction) and antibacterial use (38% reduction).
                These results clearly demonstrate that ribosomal immunostimulant is effective in preventing and in reducing upper and lower respiratory tract infections in children and adults. The efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children. Isoprinosine, an in vitro immuno-enhancing agent principally acting by stimulating T-lymphocytes, is one of a number of agents sometimes used in an attempt to prevent recurrent respiratory infections in children, although there are no formal trials for this particular drug. We performed a placebo-controlled double-blind trial to assess the efficacy of isoprinosine (50 mg/kg per day) for 6 weeks followed by 50 mg/kg per day twice weekly for 6 weeks in the prevention of frequent acute respiratory tract infections in 102 children aged 4-8 years. A total of 43 children treated with isoprinosine and 41 with placebo finished the study. Despite a transient increase in the total number of CD3+, CD4+ and CD8+ T-lymphocytes after 6 weeks of daily isoprinosine treatment, there was no difference in the number and length of duration of acute respiratory infections, number of antibiotic courses and number of days with cough, pharyngitis, rhinitis and increased body temperature (> or = 37.0 degrees C and > or = 38.0 degrees C). There were no changes in markers of T- or B-lymphocyte activation (CD25, HLA-DR, CD45RA/RO, CD23).
                Attempts at immunomodulation using isoprinosine in the dose and for the duration used may increase the total numbers of both CD4 and CD8 T-lymphocytes but is ineffective in prevention of respiratory tract infections in childhood. A double-blind, placebo-controlled trial was carried out in 33 children suffering from chronic or recurrent upper respiratory tract infections to assess the effectiveness of levamisole in reducing the number, duration, and severity of infective episodes. A weight-related dosage of levamisole was used (2.0 to 2.5 mg per kg body weight), patients taking a single dose on 1 day per week over an autumn-winter period of 4 months. The results showed that patients in the levamisole-treated group had statistically significantly fewer periods of upper respiratory tract infection and when they occurred the episodes were milder and shorter in the levamisole group and required less antibiotics. No side-effects were noted. The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind, placebo-controlled, randomized, multicentre trial, on 120 pediatric patients affected by recurrent respiratory infections. The clinical course of acute infections was favourable both in placebo and in treatment group, but recovery was quicker with pidotimod than with placebo. Antibiotic therapy and time of hospitalization were shorter in the patients taking pidotimod, and main symptomatic parameters (pharyngalgia, dysphagia, mucous membrane inflammation, adenopathy, anorexia) receded quickly. In patients receiving the drug as well as in placebo group changes in laboratory parameters, indicating recovery from the acute infectious events, were observed. A significant trend to normalization of the immune response, evidenced by chemotaxis and leukocyte phagocytosis index, was found only in patients treated with pidotimod. A significant decrease in the risk of relapses was observed in patients treated with pidotimod (35%), as well as a reduction of hospitalization (86%) and a decreased antibiotic therapy (47%). If a relapse occurred, the response of treated patients was quicker (fever, antibiotic therapy, hospitalization). These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy in case of clinically relevant disease. No side effects were observed. Only in 12 patients (5 pidotimod, 7 placebo) mild reactions were observed, but they were attributed to concomitant antibiotic treatment or other factors. No alterations in main laboratory parameters were seen.(ABSTRACT TRUNCATED AT 250 WORDS) Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children. We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months.
                Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected. They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule. Patients were followed up for 12 months, including the administration period. The trial began in July 1997 and ended in April 1999.
                The number (mean +/- SD) of ARTIs was 5.04 +/- 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 +/- 2.55 (median, 8.0) in the placebo group, with a mean difference of - 2.96 (95% confidence interval [CI], - 4.22 to - 1.7). The number of antibiotic courses was 2.46 +/- 2.08 (median, 1.5) in the treatment group vs 4.46 +/- 2.08 (median, 4.0) in the control group, a difference of - 2.0 (95% CI, - 3.14 to - 0.86). The total duration of ARTIs was 35.23 +/- 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 +/- 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of - 25.52 days (95% CI, - 37.56 to - 13.47 days), p < 0.001 by Student's t test and Mann-Whitney U test for all the items. Four patients in the OM-85 BV group had five adverse events. Only one episode of skin rash was related to the medication intake. Six patients in the control group had six adverse events.
                OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs. Respiratory tract infections (RTIs) are the most common infections in humans, and it is difficult to effectively treat patients with increased susceptibility to these ailments. LW 50020 (Luivac; Paspat oral), an oral immunomodulator consisting of the antigens of seven bacteria commonly involved in RTIs, has been developed for the induction of specific and nonspecific immune responses of the mucosa-associated lymphoid tissue. In this placebo-controlled study, the efficacy and safety of the tablet formulation of LW 50020 were evaluated in children and adults with recurrent RTIs. Tablets were taken once daily during two periods of 4 weeks each, interrupted by a treatment-free interval of 4 weeks. The main endpoint of the study, a clinical severity score that evaluated treatment benefits, was significantly lower in the second study period in patients treated with the bacterial lysate compared to patients given placebo. A comparison of the infection rates in the first and second study periods of patients treated with LW 50020 revealed a placebo-corrected reduction of 39% in children and a placebo-corrected reduction of 44% in adolescents and adults. The placebo-corrected duration of infections was shortened by 47% in children and by 55% in older patients. No serious drug-related side effects occurred. This study demonstrated that the oral bacterial immunomodulator LW 50020 is efficacious in treating patients with recurrent RTIs. Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults.
                This trial reports results of a double-masked, placebo-controlled, parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage.
                Two hundred girls (age range, 6 to 13 years) living in an orphanage entered the trial. Participants were randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months. Patients were followed up for 6 months, including the administration period. The trial began in September 1996 and finished in March 1997. Primary end points were the type and number of infections. Secondary end points included when an infection occurred, time to clinical cure, severity of infection, absenteeism from school due to an ARTI, number of antibiotics or other drugs prescribed, and duration of concomitant drug treatment.
                During the trial, patients in the OM-85 BV group experienced 143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile, 95th percentile) in the placebo group. This difference was statistically significant (P < 0.001). Participants who received OM-85 BV also showed significantly better results (P < 0.001) than participants who received placebo in terms of median duration of illness, median number of missed school days due to an ARTI, median number of antibiotic and drug courses, and median duration of concomitant treatment. There were significant differences (P < 0.05) in severity of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month. No adverse events related to the trial medications were reported. Conclusions: OM-85 BV had a preventive effect on ARTIs in the school girls, with a reduction in the antibiotic requirements and the duration of ARTIs. Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs. nan Forty two children with clinical diagnosis of recurrent high and low respiratory infections, were treated with an extract of P1 and F1 glycoproteins; fraction of Klebsiella pneumoniae, 1 g/day for one week a month for three months, according to a double-blind, randomized, parallel group trial.
                Improvement of clinical and laboratory results were compared with 44 control patients with the same age and similar sex distribution, that were treated with placebo. At the end of study, clinical analysis at 6, 9 and 12 months after the initial dose of Klebsiella pneumoniae, decreased in the number of respiratory infections, sick days, and school assistance were observed in the study group when compared with the control group (p < 0.001 in all parameters). There were not statistical significant changes in hemolytic complement, C3, C4 and immunoglobulins (IgA, IgG, IgM and IgE) levels before and after treatment and between groups. There were not observed adverse reactions to oral treatment with this extract of Klebsiella pneumoniae.
                These results suggested that the extract of Klebsiella can be used as a coadjuvant in the treatment of pediatric patients with recurrent high and low respiratory infections. Although much has been written on how to manage recurrent pharyngotonsillitis, it remains a controversial topic. The composition of normal commensal oropharynx bacteria may be disrupted by frequently using antimicrobials, by inhibiting sensitive organisms and by allowing resistant organisms to overgrowth. This may cause the recurrence of acute episodes. The aim of this study was to evaluate the efficacy of ribosomal immunotherapy in the prophylaxis of recurrent pharyngotonsillitis.
                A total of 160 children aged between 5 and 14 years with recurrent pharyngotonsillitis were ramdomized to receive either ribosomal immunotherapy (group A one tablet a day, 8 days a month for 3 months) or a placebo (group B same dosage for the same period).
                At the end of the study, each patient treated with Immucytal presented a subjective decrease of symptoms. Compared with group B, group A experienced a significant improvement of some clinical parameters.
                The results show that ribosomal immunotherapy causes a significant improvement of both specific and non-specific immunity and may be effective in the prophylaxis of recurrent pharyngotonsillitis and in preventing recurrences without entailing side effects or bacterial resistance. Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children. As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children.
                This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs. Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5. URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic.
                OM-85-treated patients had a lower rate of URTIs (p < 0.05). The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo. The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively. The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year. Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05).
                OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs. Safety and tolerance of test medication were good, comparable to placebo. The effect of a bacterial extract orally administered to 20 children with recurrent infections of the upper respiratory tract, was investigated in a double-blind study. The composition of the peripheral blood mononuclear cells (T and B-lymphocytes, monocytes) and some of their biochemical properties (5'-nucleotidase, beta-N-acetyl-glucosaminidase and non-specific esterase) were unaffected. In contrast, the allogeneic mixed lymphocyte reaction was significantly increased in patients treated with the bacterial extract. In the treated group the number of infectious episodes decreased significantly and the clinical response correlated positively with the mixed lymphocyte reaction. These findings suggest that the bacterial extract has the capacity of restoring depressed immune functions by acting through the gut-associated lymphoid tissue. The effectiveness of an orally administrable thymic derivative (Thymomodulin) for the treatment of the recurrent respiratory infections (RRI) in children has been studied in a double-blind clinical trial with historical comparison. In the Thymomodulin treated group a significant decrease of the monthly frequency of RRI has been observed in comparison with the previous year (P less than 0.05) and with the placebo treated group (P less than 0.002). The evaluation of the laboratory data at the beginning of the study didn't show in the two groups typical alterations of the common hematological and immunological parameters, but at the end of the trial a statistically significant increase of the levels of salivary IgA has been noticed only in the Thymomodulin treated group (P less than 0.02). Fifty-one children aged 4-12 years, presenting with an acute epidose of chronic rhinosinusitis, were treated for 6 months with either Broncho-Vaxom (BV; marketed in Yugoslavia under the trade mark of Broncho-Munal) or placebo under double-blind randomized conditions. The efficacy of BV was assessed on the basis of clinical symptoms (cough, nasal discharge, congestion of nasal mucosa), number and duration of concomitant treatments (antibiotics, secretolytics, antitussives), number and duration of acute episodes during the trial and serum IgA levels. In BV treated patients the incidence and duration of infectious episodes and the number and duration of concomitant treatments decreased significantly in comparison with the placebo group, and the clinical response correlated positively with an increase in the serum levels of IgA. The results of treatment of acute episodes of chronic rhinosinusitis in children demonstrated the curative and prophylactic efficacy of BV. 70 children with chronically relapsing mild-to-severe upper-respiratory-tract infections during autumn and winter participated in a six month double-blind placebo-controlled trial: 38 of them received about 1-25 mg/kg of levamisole twice daily for two consecutive days every week, the others were given placebo. During each of the three trial periods, levamisole proved superior to placebo in that it significantly reduced the number, the duration, and the severity of the infections. Moreover, in the group treated with the higher dose (i.e. greater than 2-5 mg/kg/day), the superiority of levamisole to placebo was much more clear-cut. No drug-related side-effects were reported. A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age. The therapeutic efficacy of the synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind placebo-controlled study in parallel groups in the management of recurrences in 235 children with recurrent tonsillitis. The ambulant study provided for 15 days of treatment with two oral vials of pidotimod 400 mg or placebo daily, in accordance with a randomisation list, 60 days of treatment with one oral vial of pidotimod 400 mg or placebo daily, and a 90-day follow-up period. The total trial period was 165 days. In addition to evaluating the number of tonsillitis recurrences which occurred during the 75 days of treatment and the 90-day follow-up period, the number of days on which the principal symptoms of the illness were present and on which drugs such as antibiotics or anti-inflammatory agents were used concomitantly, as well as the number of days' absence from school, were analyzed. The findings showed that, taking the treatment phase and the three-month follow-up period together, pidotimod significantly reduces the incidence of inflammatory upper airways episodes. The very low incidence of adverse effects, which was the same as that in the placebo group, confirmed the excellent safety of the product. Echinacea is a widely used herbal remedy for treatment of upper respiratory tract infections (URIs). However, there are few data on the efficacy and safety of echinacea in treating URIs in children.
                To determine if Echinacea purpurea is effective in reducing the duration and/or severity of URI symptoms in children and to assess its safety in this population.
                Randomized, double-blind, placebo-controlled trial of healthy children 2 to 11 years old recruited from a regional practice-based network and an alternative medical center in 4-month periods from 2000 through 2002.
                Study patients were randomized to receive either echinacea or placebo for up to 3 URIs over a 4-month period. Study medication was begun at the onset of symptoms and continued throughout the URI, for a maximum of 10 days.
                Primary outcomes were duration and severity of symptoms and adverse events recorded by parents; secondary outcomes included peak severity of symptoms, number of days of peak severity, number of days of fever, and a global assessment of severity of symptoms by parents of study children.
                Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs treated with echinacea and 370 with placebo. There were 79 children who completed their study period without having a URI. The median duration of URIs was 9 days (95% confidence interval, 8-10 days); there was no difference in duration between URIs treated with echinacea or placebo (P =.89). There was also no difference in the overall estimate of severity of URI symptoms between the 2 treatment groups (median, 33 in both groups; P =.69). In addition, there were no statistically significant differences between the 2 groups for peak severity of symptoms (P =.68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in the placebo group; P =.97), number of days of fever (0.81 in the echinacea group vs 0.64 in the placebo group; P =.09), or parental global assessment of severity of the URI (P =.67). Overall, there was no difference in the rate of adverse events reported in the 2 treatment groups; however, rash occurred during 7.1% of the URIs treated with echinacea and 2.7% of those treated with placebo (P =.008).
                Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash. 120 children, 71 male and 49 female, aged between 2 years and 15 years (mean 6.15 +/- 3.52 years) with recurrent respiratory infections, were treated with Immucytal, an immunomodulator of bacterial origin, based on membrane proteoglycan fractions plus bacterial ribosomes. The children, selected on the basis of the previous year's clinical score, were treated according to a random design with either Immucytal or placebo, using the same dosage of one puff per nostril plus one puff in the oropharyngeal cavity three times a day, as follows: 1st month: two weeks' treatment, one week wash out, one week's treatment. 2nd, 3rd, 4th months: two weeks' treatment, two week's wash out. Monthly throughout the treatment period the frequency and severity of airway infections episodes were assessed using the same score as for admission. Blood chemistry test, immunological assays (circulating Ig, lymphocyte subpopulations, Merieux Multitest in vivo blastization test) and respiratory tests (spirometry using a pneumotachigraph) were done before and after the treatment. 118/120 children completed treatment; the two dropouts were in the placebo group, one for compliance and the other because of headaches. Respiratory symptoms improved significantly in the actively treated children already from the first month, but not in the placebo group. This improvement consisted of reduction of the respiratory infectious episodes in both the upper and lower airways. No changes were noted in respiratory function parameters. From the immunological viewpoint, there were significant rises in serum IgA and IgM and enhanced skin response tot he Multitest; there was no change in the percentages of different circulating lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS) Recurrent otitis media is a common problem in young children. Echinacea and osteopathic manipulative treatment have been proposed as preventive measures, but have been inadequately studied. This study was designed to assess the efficacy of Echinacea purpurea and/or osteopathic manipulative treatment (OMT) for prevention of acute otitis media in otitis-prone children.
                A randomized, placebo-controlled, two-by-two factorial trial with 6-month follow-up, conducted 1999 - 2002 in Tucson, Arizona. Patients were aged 12-60 months with recurrent otitis media, defined as three or more separate episodes of acute otitis media within six months, or at least four episodes in one year. Ninety children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which 84 had follow-up for at least 3 months. Children were randomly assigned to one of four protocol groups: double placebo, echinacea plus sham OMT, true OMT (including cranial manipulation) plus placebo echinacea, or true echinacea plus OMT. An alcohol extract of Echinacea purpurea roots and seeds (or placebo) was administered for 10 days at the first sign of each common cold. Five OMT visits (or sham treatments) were offered over 3 months.
                No interaction was found between echinacea and OMT. Echinacea was associated with a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI 1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus 61%; relative risk, 0.72, 95% CI 0.48, 1.10).
                In otitis-prone young children, treating colds with this form of echinacea does not decrease the risk of acute otitis media, and may in fact increase risk. A regimen of up to five osteopathic manipulative treatments does not significantly decrease the risk of acute otitis media.
                ClinicalTrials.gov Identifier: NCT00010465. Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels.
                This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment.
                IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients.
                This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV. To elucidate the prospects administration of allicor (long-releasing garlic tablets) in prevention of acute respiratory diseases (ARD) in children vs benzimidazole (dibazole).
                At the first stage, tolerance of allicor (600 mg/day) and its effects on ARD morbidity were investigated in an opened 5-month study in 172 children aged 7-16 years compared to 468 controls. As the second stage, the effects of allicor (300 mg/day) on ASRD morbidity were investigated in a double-blind placebo-controlled randomized 5-month trial in 42 children aged 10-12 years in comparison with 41 placebo-treated children and 73 benzimidazole-treated children.
                At the first stage of the study allicor was not observed to induce gastrointestinal side effects in children at any dosage while ARD morbidity was reduced 2-4-fold as compared to the controls. At the second stage of the study allicor reduced ARD morbidity 1.7-fold compared to placebo and 2.4-fold vs benzimidazole. There was no significant difference in ARD morbidity between placebo- and benzimidazole-treated groups. Health index in allicor-treated group was 1.5-fold higher as compared either to placebo- or benzimidazole-treated children.
                Thus, the results of this study have demonstrated that allicor is effective for non-specific prevention of acute respiratory infections in children and has no side effects. ARD prevention with benzimidazole appeared ineffective in placebo-controlled study, so the development of new useful and safe preparations is of ultimate importance. A controlled trial was undertaken to test I.R.S. 19 (a commercial intranasal spray) versus placebo in the prevention of acute respiratory diseases (ARD) in 825 maternity-school children in three cities; another control group of 327 children received neither I.R.S. 19 nor placebo. The spraying was done twice a day for a total of 20 spraying days in each child; sprayings were interrupted on weekends and during absence, the mean spraying period being 34 calendar days. During the 6-month study (1 November to 30 April) the children were monitored for ARD morbidity causing absence from school. A total of 1,585 such ARD cases occurred; their etiology was not investigated. The indices evaluated were: total duration of ARD-associated absence, ARD incidence, and mean duration of one illness. With the administration schedule used, I.R.S. 19 did not, in an overall evaluation, surpass placebo in any of these indices in either normal children or a subgroup of children with presumed enhanced ARD susceptibility. nan In a double-blind placebo controlled study of levamisole in the treatment of children with recurrent upper respiratory tract infection (URI) eighty-six patients took part. Medication was given once a week, in a single body-weight adjusted dose. The children treated with levamisole had a statistically significantly reduced incidence of episodes of infection which were severe, less prolonged and required less antibiotics. No side-effects were reported. The efficacy and safety of a new synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in recurrent infections of the primary airways were assessed in a group of 416 children with a history of recurrent respiratory infections (RRI). This was a double-blind randomized trial of pidotimod vs. placebo, consisting of a treatment period of 60 days and a follow-up period of 3 months. A reduction in the duration and frequency of infectious episodes in the group of children treated with pidotimod (one 400 mg oral bottle daily) was observed which was statistically different from the placebo group. The protective effect produced by pidotimod was also confirmed by a series of recordings made over the five-month observation period, which showed a significant reduction in the number of days of fever, the severity of the signs and symptoms of acute episodes, use of antibiotics and antipyretic drugs and absence from school or nursery school. Safety was excellent. The aim of this study was to compare the efficacy and the safety of a short oral ribosomal immunotherapy (Immucytal) in the prevention of chronic otitis media in children. Seventy-two patients were enrolled in this study, 41 males and 31 females, aged between 6 and 14 years, with an history of recurrent otitis media. Patients were randomised to receive Immucytal (group A) or placebo (group B) according to the following protocol: one tablet daily in the morning 8 days per month for three consecutive months. Immucytal and placebo were identical in shape and size, in order to maintain double-blind conditions. The efficacy parameters were (evaluated before, at the end and 6 months after the beginning of the therapy): clinical score; changes in immunological parameters; patient's parents assessment of symptoms on a scale from 0 (much worse) to 4 (much improved) and hearing tests. Patients of group A, had an improvement of clinical items measured, serum concentrations of immunoglobulins, subjective patient's parents assessment of symptoms and hearing tests. For all evaluations, a significant difference between treatment groups was found. Using this dosage and posology (shorter than others) the beneficial effects of Immucytal were maintained until the end of the 6-month study period. To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period.
                Randomized, double-blind, placebo-controlled study.
                Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215).
                Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks.
                Significant mean +/- SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 +/- 1.1 vs 1.8 +/- 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 +/- 2.9 vs 5.4 +/- 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient.
                A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed. The therapeutic activity and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new synthetic "biological response modifier", were examined in a double-blind, placebo-controlled, multicentre trial in 101 children, including 53 boys and 48 girls aged 2-13 years (mean +/- SD: 4.7 +/- 2.1 years) with a history of recurrent respiratory infections (RRI). Pidotimod (400 mg/day) or placebo were administered orally for 60 consecutive days, followed by a further 60-day follow-up period. The trial was completed by 89.1% of patients. The results indicate that pidotimod has a beneficial effect in children with recurrent respiratory infections: the percentage of patients presenting symptoms affecting the upper and lower airways was significantly lower after treatment with the active drug than after treatment with placebo. Relevant side effects were not reported during the trial. An evaluation of the expression of CD25 (after in vitro stimulation of circulating mononuclear cells with PHA) before and after treatment with the two products revealed a significant increase in CD25+ cells in the group treated with pidotimod but not in the group treated with placebo. The aim of this study was to evaluate the efficacy of an oral ribosomal immunotherapy in the management of children with recurrent acute adenoiditis (RAA). 60 children with RAA were included and randomly assigned into two groups (group A and B). Group A children underwent ribosomal prophylaxis, while group B received a placebo. Before, at the end and 6 months after start of the therapy, children underwent medical history, ENT examination, plasma levels of immunoglobulins class E, A, G, M (IgE, IgA, IgG, IgM), tympanometry, active anterior rhinomanometry and VAS scores by children' parents. After the treatment and at the end of the study, in the group A, the serum concentration of IgE was significantly (P < 0.05) lower than in group B (77.34 +/- 6.23 vs. 95.49 +/- 7.07 mg/dl; 74.82 +/- 6.26 vs. 94.44 +/- 7.44 mg/dl), IgA titers were significantly (P < 0.05) higher than in group B (312.04 +/- 18.41 vs. 213.20 +/- 11.82; 309.07 +/- 18.33 vs. 211.73 +/- 11.54 mg/dl) as well as serum concentration of IgG (1401.12 +/- 118.81 vs. 1101.81 +/- 109.64 mg/dl; 1412.19 +/- 116.43 vs. 1144.06 +/- 103.58 mg/dl). At the end of the study, comparison between the two groups showed, in group A: 77% of children (n = 23), versus 23% (n = 7) of group B, with a type A tympanogram; significant (P < 0.05) nasal flow decrease at the rhinomanometric measures; VAS scores were significantly (P < 0.05) improved (1.8 +/- 0.22 vs. 5.1 +/- 0.59) and frequency, severity and social impact of RAA episodes were significantly (P < 0.05) lower than group B. Our results show the therapeutic effectiveness of this approach in the prophylaxis of recurrent acute adenoiditis. 94 children suffering from frequent infections of the respiratory tract and of the ear, nose and throat were treated under double-blind conditions with either a bacterial lysate (n = 45) or a placebo (n = 49). During the 6 months of the trial both treatments brought about a significant decrease in the incidence and duration of these infections as well as in the duration of concomitant antibiotherapy in comparison to the corresponding prior 6-month reference period. As these positive results recorded under the bacterial lysate and the placebo could not be differentiated statistically, the influence of meteorological and epidemiological factors as well as of the age of the children is discussed. Respiratory tract infections are among the most common diseases both in adults and children.
                This multicentre study, was carried out in 212 patients (118 adults with chronic respiratory diseases and 94 children with recurrent respiratory infections) at six Italian study centres. It was performed to establish the efficacy of Lantigen B for the prevention of bacterial complications and/or reduction of associated symptoms. Lantigen B is an oral product based on bacterial lysates of six different inactivated strains commonly involved in respiratory tract infections.
                The results of prophylactic treatment with Lantigen B in the population investigated were as follows: - the mean incidence of recurrence in the pediatric patients over the 6-month observation period of the study was 1.643 in the placebo group and 1.211 in the Lantigen B group (a relative reduction of 35.7%); - the mean incidence of recurrence in the adult patients over the 6-month observation period of the study was 0.73 in the placebo group and 0.56 in the Lantigen B group (a relative reduction of 30.4%). The improvement in other important parameters, such as the number of days with a high temperature, cough, and catarrh in the children and objective clinical findings at the lymph nodes of the neck, chest, and pharyngotonsillar region in the adults, provides further evidence of the efficacy of Lantigen B.
                This study demonstrates Lantigen B's effectiveness in the prevention of bacterial complications and suggests that it can be used in patients who are particularly at risk of infection (children, the elderly, diabetics, and immunocompromised patients) or those in whom an infection might aggravate a clinical picture that is already inherently complicated (diabetics again, but also patients with heart, kidney, or liver disease). nan nan 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. Levamisole was tested double-blind in 106 children with recurrent upper respiratory tract infections. They received either levamisole (n = 53) or placebo (n = 53) 0.5 ml/kg bodyweight b.i.d. for two consecutive days each week for six months. A control examination was performed every two months. Both groups were compared by means of the Fisher-test and the Mann-Whitney U-test (two-tailed probability each). Improvement was observed more frequently in the levamisole group with regard to the number of episodes of infection, and the total duration and severity of the infections. No side-effects, except for some stomach complaints in one levamisole patient, were reported. Reaferon, the analog of human alpha 2-interferon obtained by gene engineering techniques, was studied with a view to its use for the prevention of hepatitis A. The study involved children of preschool age in Tashkent. In a strictly controlled trial children aged 2-6 years received the preparation orally in a dose of 1 X 10(6) I. U. or the diluent alone used as placebo. The preparation was administered to 1,100 children and the placebo to 1,078 children. The preparation and placebo were administered twice a week for two months. On the whole, during that period hepatitis A morbidity in both test and control groups of children was the same (5.1% and 4.9% respectively), but among children of nursery age receiving Reaferon the incidence of hepatitis A and acute respiratory viral infections was lower than among those receiving the placebo, though this difference was statistically significant only for cases of acute respiratory infections. Numerous trials of prophylaxis of recurrent respiratory infections in children have been performed, even though the only controlled trials providing incontrovertible results were the ones carried out with levamisole and thymostimulin through intramuscular administration. We have experimented a calf-thymic extract administered by oral route (thymomodulin). During the summer we enrolled 40 children aged between 3.5, and 9 years who had suffered from RRI during the previous winter. The patients were randomly divided in two groups and respectively treated with thymomodulin or with placebo; 21 children were given the thymic extract and 19 the placebo. The trial was carried out according to a double-blind schedule for a period of four months, from the beginning of October '84. At the end of the trial we assessed the catharral bouts observed during the research period by the family doctors and the parents evaluation on the clinical state. The difference between the two groups is statistically highly significant both with reference to the reduction of the total number of catharral bouts and to the general clinical state according to the parents opinion. The research clearly demonstrates the protective effect of the thymomodulin, probably due to the "restorative" effect on some immunological functions, temporarily compromised during the infection bouts. A 6-month double-blind, prospective, randomized, placebo-controlled trial was conducted to establish the safety and efficacy of OM-85-BV in the treatment of subacute sinusitis and in the following prevention of the respiratory tract infections in 56 children from 18 months to 9 years of age. In the subacute phase of the sinusitis the patients were given one OM-85-BV capsule (3.5 mg of bacterial extracts) (n = 26) or placebo (n = 30), daily for ten days; additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three divided doses for 21 days. For the following two months the patients took one OM-85-BV capsule or placebo, ten days a month. In the subacute phase the OM-85-BV group of patients improved sooner (5.56 +/- 4.98 vs 10 +/- 8.49 days) and had a shorter convalescence (15.38 +/- 8.91 vs 20.28 +/- 7.17 days). During the six month follow-up the patients in the OM-85-BV group had a lower number of infections (1.56 +/- 0.3 vs 2.22 +/- 0.43) and required a lower number of drug treatments (1.47 +/- 0.32 vs 1.94 +/- 0.42). One patient treated with OM-85-BV presented a mild rash which disappeared three days after the drug discontinuation. We conclude that OM-85-BV is safe at pediatric ages, as well as accelerates the cure and improvement of subacute sinusitis while it lowers the incidence of respiratory infections.
This review shows that IS reduce the incidence of ARTIs by 40% on average in susceptible children. Studies in healthy children are not available. Although the safety profile in the studies was good, some IS may be unsafe. ARTI-susceptible children may benefit from IS treatment. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicentre, double-blind, placebo-controlled RCTs on the role of IS in preventing ARTIs in children.