Prevention Of Recurrent Respiratory Infections Research Articles

Reappraisal of Pidotimod: an immunomodulatory agent with 30-year evidence.

Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) is a synthetic dipeptide with immunomodulatory properties that is indicated for use in adults and children over 3 years of age with documented cell-mediated immunodepression during respiratory and urinary tract infections. Infections are associated with an immune response that helps fight pathogens. In this scenario, inflammatory events occur to improve the antimicrobial reaction. However, defective immunity and/or sustained inflammation may adversely affect the course of the infection. Thus, modulating immune function could be a valuable option in managing patients with infections. The multifaceted mechanism of action of Pidotimod enables it to modulate innate and adaptive immunity. Extensive evidence about Pidotimod, accumulated over the last 30 years, has provided much data on the prevention of recurrent respiratory infections in susceptible children and respiratory exacerbations in patients with chronic bronchitis. Recent studies provide interesting information on how Pidotimod affects the metabolomic profiles of patients with bronchiectasis, clinical and immunological outcomes of elderly patients with pneumonia, clinical and cellular changes in patients with allergic rhinitis and asthma, and beneficial effects on cytokines and humoral immunity in human immunodeficiency virus (HIV) patients. Preliminary experience suggests that Pidotimod can shorten the duration of COVID-19 infection and reduce clinical severity by modulating the immune response, as well as prevent vaccination-related adverse events. In conclusion, the immunomodulatory properties of Pidotimod indicate that it may be a valuable option in managing patients with respiratory infections and other immune-mediated disorders, including allergy, chronic obstructive pulmonary disease, and asthma.

Lactoferrin in the Prevention of Recurrent Respiratory Infections in Preschool Children: A Prospective Randomized Study.

Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control (n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0-2] vs. control (2, IQR: 1-3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf (n = 1, 4%) vs. control (n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06-0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use.

Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies.

Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved mechanisms. OM-85 is the product whose anti-viral effects have been most extensively studied in vitro, animal, and human cell studies and in translational animal infection/disease models. The results of the latter studies, describing the potential immune training-based activities of such BL, leading to the protection against respiratory viruses, will be reported. In response to human rhinovirus, influenza virus, respiratory syncytial virus and severe acute respiratory coronavirus-2, OM-85 was effective in modulating the structure and the functions of a large numbers of airways epithelial and immune cells, when administered both orally and intranasally.

Risk factors for recurrent respiratory tract infections and acute respiratory failure in children with spinal muscular atrophy.

Assessment of and intervention for sleep-disordered breathing and malnutrition are related to the prevention of recurrent respiratory tract infections (RRTIs) and acute respiratory failure (ARF) in children with spinal muscular atrophy (SMA). However, specific standards for sleep-disordered breathing and malnutrition in the prevention of RRTIs and ARF have not been clarified. The study aimed to identify the risk factors and predictive indices for RRTIs and/or ARF in children with SMA. In this retrospective study, the differences in clinical characteristics between patients with and without RRTIs and ARF were compared, and binary logistic regression analysis was carried out. The optimal cutoff points for positive predictors were obtained. SMA type 1 (odds ratio (OR) = 5.21, 95% confidence interval (CI) 1.50-18.17, p = 0.010) and the apnea-hypopnea index (AHI) (OR = 1.12, 95% CI 1.01-1.24, p = 0.026) were risk factors, while the body mass index z score (BMIz) (OR = 0.65, 95% CI 0.46-0.91, p = 0.013) and mean pulse oxygen saturation (MSpO2 ) (OR = 0.72, 95% CI 0.52-1.00, p = 0.049) were protective factors. A standard consisting of (i) MSpO2 < 96% and (ii) AHI > 10 events/h and/or BMIz < -1 predicted the occurrence of RRTIs and/or ARF in the next year with a sensitivity of 0.513 and a specificity of 0.957. SMA type 1, BMIz, AHI and MSpO2 should be used to estimate the risk of RRTI and/or ARF in children with SMA. MSpO2 < 96% combined with AHI > 10 events/h or BMIz < -1 should be used as the intervention standard.

RETROSPECTIVE ANALYSIS OF PREDICTOR OF RECURRENT RESPIRATORY INFECTIONS IN PRESCHOOL CHILDREN

Among the current trends in the systemic prevention of recurrent respiratory infections in preschool children is the differentiated detection and clustering of the most significant ante- and prenatal factors associated with frequent acute respiratory infections. Thus, a comprehensive retrospective investigation of such factors in terms of their association with the integral indicators of acute respiratory infections recurrence in preschool children is exceptionally relevant. The study of particular manifestations of undifferentiated connective tissue dysplasia during recurrent respiratory infections is of great clinical and social relevance. This study research aims at determining the levels of inter-dependency between recurrence indicators of acute respiratory infections in preschool children and ante- and prenatal predictors analyzed retrospectively. Fifty-one children (24 boys and 27 girls) aged 1 to 6 years old, undergoing inpatient treatment for acute respiratory infection, were involved in the clinical study. Two markers of acute respiratory infection recurrence (infection index, resistance index) and dolichostenomelia integral indicator, which is used as the marker of external signs of connective tissue undifferentiated dysplasia, were calculated for each child. In addition, the retrospective analysis of 67 ante- and prenatal factors directly related to the children were examined. The statistical processing of the obtained digital material was performed by IBM SPSS Statistics 26 licensed software. Only non-parametric statistics methods were applied in the purpose.&#x0D; The first stage of investigating the inter-dependency between the acute respiratory infections frequency, the particular manifestations of undifferentiated connective tissue dysplasia, on the one hand, and the ante- and prenatal predictors, on the other hand, was carried out. The results obtained provided the grounds for the further research in the outlined direction involving the higher number of patients and using the more sensitive statistical methods. The higher infectious index values in the preschool children correlate with the following factors as lower initial overall age of their parents, smaller number of their mothers’ previous pregnancies, larger mothers’ body weight at the beginning of pregnancies, longer deliveries, lower Apgar scores in the newborns and no vaccination for tuberculosis. The resistance index values in the examined children increase with the simultaneous decreasing in the haemoglobin concentration in the mothers’ blood just before the deliveries and in cases of no vaccination in newborns for tuberculosis. The dolichostenomelia integral indicator in the patients aged from 1 to 6 years directly correlates with their age as well as with such retrospectively studied predictors as the newborns body mass index, the presence of foetoplacental insufficiency and the total number of complications caused by connective tissue dysplasia in their mothers during the pregnancies and deliveries.

Is it possible to prevent respiratory pathology?

Acute respiratory infections are the most common reason to consult a paediatrician. Children, especially during critical periods of immune response, are one of the most vulnerable groups to infections. The prevention of recurring respiratory infections is very important, especially from the beginning of attending pre-school and school facilities. Since ancient times, preventive measures such as rational daily routine, sufficient physical activity, correction of nutritional status, phytotherapy and homeopathic treatment have been used. In recent years these children have been optimising their vitamin D status and taking antioxidant vitamins, micro- and macronutrients. To date, as a result of innovative research on the human microbiome, information has emerged on its impact on the human body as a whole. The connection of the intestinal microbiota with the brain (gut-brain axis), with the respiratory tract (gut-lung axis), the cardiovascular system, kidneys and even mental health has been proved. The use of multistrain and multispecies probiotics in the prevention of recurrent infections in children opens up new opportunities to influence the child’s immune response and to form food tolerance. Today, a new multistrain multispecies probiotic (manufacturer ADM Protexin, UK) for the prevention of recurrent respiratory infections in children has appeared on the market. Studies have shown that using several strains of lactobacillus contained in this probiotic leads to more consistent results than monostrains and placebo in the prevention of respiratory diseases. Given the problem of antibiotic resistance, especially in young children, the new possibilities of preventing acute respiratory diseases in children using multistrain and multispecies probiotics make it possible not only to reduce the number and severity of episodes of acute respiratory infections, but also to reduce the frequency of antibiotic use.

Effectiveness of the probiotic B. bifidum 1 for the prevention of recurrent respiratory infections in children of 7–11 years old with functional and chronic disorders of gastrointestinal tract

Background: Acute respiratory infections (ARI) are a significant public health problem worldwide due to their high incidence and lack of specific prevention for most of them. Previous systematic reviews have demonstrated the possibility to use probiotics to prevent ARI in children. The prophylactic efficacy of the B. bifidum 1 strain in patients with recurrent ARI has not been investigated specifically against the background of concomitant gastrointestinal disorders, which may affect the effectiveness of probiotic therapy. Aim: To evaluate the effectiveness and safety of the sorbed probiotic B. bifidum 1 for prevention of ARI in children of 7 to 11 years of age with functional intestinal disorders or gastritis / gastroduodenitis. Materials and methods : This prospective, randomized, open-label study was completed by 44 children divided into two parallel groups: with and without administration of the sorbed B. bifidum 1 at 5 × 10 7 CFU three times daily for 21 days as a component of a comprehensive sanatorium treatment for recurrent ARI. The children were followed up for three months after the end of the treatment in a winter season, with assessment of frequency, severity and duration of ARI episodes. Results: The use of B. bifidum 1 in children of 7–11 years old with functional and chronic gastrointestinal disorders reduced the incidence of upper respiratory tract infections (relative risk reduction 0.48, 95% confidence interval 0.15–0.68) and mean duration of respiratory diseases by 2.26 days (95% confidence interval 0.23–4.27). It also reduced fever, frequency of cases with cough and the need in antibiotic therapy. The efficacy was related mainly to a decrease in the number of children with more than one ARI episode during the three months of the winter season. Conclusion: The results of probiotics use should be evaluated with consideration of underlying disease, which can more clearly indicate the size of their effect. The use of probiotics for prevention of infectious diseases, including respiratory infections, in children with functional and chronic gastrointestinal disorders can be promising in reduction of the overall morbidity and requires further studies.

Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma.

Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control). The authors determined that treatment with pidotimod exacerbated pulmonary inflammation as demonstrated by significantly increased eosinophil infiltration, dramatically elevated immunoglobulin E production, and enhanced T helper 2 response. Moreover, treatment failed to attenuate mucus production in lung tissue, and did not reduce OVA‑induced high levels of FIZZ1 and Arg1 expression in asthmatic mice. In contrast, administration of dexamethasone was efficient in alleviating allergic airway inflammation in OVA‑induced asthmatic mice. These data indicated that pidotimod as an immunotherapeutic agent should be used cautiously and the effectiveness for controlling allergic asthma needs further evaluation and research.

How French general practitioners manage and prevent recurrent respiratory tract infections in children: the SOURIRRE survey.

BackgroundRecurrent respiratory tract infections (RRTIs) are the most common reason for children’s visits to primary care physicians in France; however, little is known about general practitioners’ (GPs) opinions and expectations concerning the management and prevention of these common and recurrent pathologies.PurposeTo describe French GPs’ daily practice in the management of respiratory infections and the prevention of their recurrence in children.MethodsA sample group of French GPs answered a structured questionnaire on risk factors, RRTI management, antibiotic use and prevention measures.ResultsA total of 358 GPs participated in the survey. Rhinopharyngitis, the most frequent respiratory infection, was considered to be recurrent if six or more episodes occurred in a year. Four risk factors were acknowledged as substantial: living in communities, passive smoking, pollution and allergies. Around 63% of GPs said that RRTIs are too often treated with antibiotics. More than 85% thought that prevention of RRTIs is possible. Smoking cessation, vaccination, allergen avoidance and hygiene were identified as the main preventive measures. A large majority of GPs (84%) prescribed products for prevention and ~90% would prescribe a product stimulating immunity if the efficacy and tolerability of these agents was proven and confirmed in their daily practice.ConclusionsFrench GPs are well aware of the health and socioeconomic burdens resulting from RRTIs, as well as the risk of antibiotic overuse. They have a prevention-oriented approach, implement preventive measures when possible and prescribe products for prevention.

Judgement, prevention and treatment of recurrent respiratory tract infections in children

Recurrent respiratory tract infections(RRIs) is a common clinical presentation in paediatrics and represent a huge burden of children health, family life and socioeconomic costs.Nowadays, the definition of pediatric RRIs has not been reached a consensus in the international field.Diagnosis and treatment of pediatric RRIs present a muddled picture clinically.This review introduces the definition and judgement, pathogeny and risk factors, classification, principle of management and prevention of pediatric RRIs in order to provide a reference for clinical practice of pediatrician. Key words: Recurrent respiratory tract infection; Pathogenesis; Prevention; Child

Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study.

Acute respiratory infections (ARI) still represent a big challenge for paediatricians, especially in those children defined as "ailed" as they are more susceptible to such kinds of disease. In this paediatric population, the immune system is still under-developed with an evident alteration in cytokine levels. A clinical study was carried out in 5 sites in Russia with the intention to enroll children particularly susceptible to contract respiratory infections (defined as "ailing"), assigning them to a treatment group with pidotimod in comparison with a control group, treating them for 30 days and observing the reduction in the number of ARI episodes throughout the follow-up period (6 months). Moreover, changes in serum immunological markers were evaluated at baseline and 30 days after treatment discontinuation. One hundred and fifty-seven ailing children were enrolled and assigned to two arms: a main pidotimod treatment group or a control group. The percentage of incidence of ARIs in the observation period at three different time points was statistically significant (p < 0.05). At the end of the follow-up period (after 6 months), ARIs had developed in 72 children (92.3%) in the main group and in 79 patients (100%) in the control group. Concerning changes of the immunological markers, the treatment group showed a better profile of normalization compared to the control group. The 30-day pidotimod therapy course led to improvement/reduction in the rate of acute respiratory infection recurrence in ailing children within a 3-month period, with a quick elimination of symptoms and signs of infection and, as a result, a faster recovery. The normalisation of the content of the pro-inflammatory cytokine interleukin-8 confirmed the immune-modulatory effect of the investigational drug, underlying its prophylactic effect.

Bacterial Extracts as Immunomodulators for the Prevention of Recurrent Respiratory Infections in Children

Acute respiratory tract infections (ARTI) are the more frequent causes of morbidity and mortality in children. This review was conducted to assess the existing evidence concerning bacterial extracts efficacy in the prevention of pediatric ARTI. The data sources for the identification of clinical trials and reviews included principal bibliographic databases (MEDLINE, Embase, Cochrane Library, PubMed/www.ncbi.nlm.nih.gov). Selected clinical trials only involved children suffering from recurrent ARTI. Bacterial extracts may reduce the incidence of ARTI of about 40% in toddlers (2-5 years), school boys (6-12 years) and children at higher ARTI risk (e.g. children living in orphanages). Among others, the active treatment with OM-85 led to 26, 2% fewer patients with recurrent ARTI. Data from the literature are encouraging, particularly for treatment with OM-85. The strengthening of pre-clinical and clinical research is necessary to allow routine recommendation of bacterial extracts prescription for ARTI prevention in children.

Salso-Sulphide Thermal Water in the Prevention of Recurrent Respiratory Infections in Children

Recurrent respiratory infections (RRI) represent a social problem for both the pharmaco-economic impact and the burden on the family. Thermal water is popularly well accepted. However, there is no scientific evidence of its preventive activity on recurrent respiratory tract infections (RRI). Therefore, the purpose of this study was to evaluate the effects of Agnano thermal water nasal irrigation on RRI prevention in children.A total of 107 children (70 males, mean age 4.5 plus minus1.2 years) with RRI were enrolled in the study. At baseline, children were randomly assigned to the treatment with: A) inhaled crenotherapy with salso-sulphide water or B) isotonic saline (NaCl 0.9 percent). Inhaled therapy was performed using nasal washing by Rino-jet (ASEMA srl, Milan, Italy) b.i.d. for 12 days. Nasal washing lasted 2 minutes per nostril. Immediately before washing, children inhaled 1 l of water by stream inhalation per 2 minutes. Crenotherapy was capable of significantly reducing: the number of respiratory infections, nasal symptoms, neutrophil and bacteria count, turbinate and adenoidal hypertrophy, presence of biofilm, and blockage of ostiomeatal complex (OCM). In conclusion, this study provides the first evidence that Agnano crenotherapy may be capable of preventing RRI in children as it exerts some positive effects, such as reduction of nasal obstruction, OCM blockage, biofilm, and inflammatory events.

Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: A meta-analysis

BackgroundRespiratory tract infections are common and remain a major source of morbidity, mortality and economic cost worldwide, despite advances in modern medicine. One treatment approach is to non-specifically increase the immune response or augment innate defense mechanisms through the use of bacterial lysates. Polyvalent Mechanical Bacterial Lysate (PMBL) is a bacterial lysate made from a wide range of pathogenic bacteria, including all of the most commonly occurring pathogens of the upper and lower respiratory tract obtained by mechanical lysis. AimTo test the available evidence that PMBL is able to prevent respiratory tract infections. MethodsA number of studies investigating randomized comparisons of PMBL (active) with placebo or no treatment (control) were selected for analysis. The primary outcome measure was the prevention of exacerbations or acute respiratory tract infection. The results were expressed as relative risk (RR) and the number of patients needed to treat for one to benefit (NNTB). ResultsData from 2557 patients from 15 randomized clinical trials (RCTs) was investigated. PMBL induced a significant reduction of infections vs placebo (RR −0.513; 95% CI; −0.722 – −0.303; p = 0.00). The NNTB was 1.15. The RR was always in favor of PMBL (in recurrent respiratory infections other than COPD, chronic bronchitis and tuberculosis, RR −0.502; 95% CI −0.824 – −0.181; in children RR −2.204; 95% CI −3.260 – −1.147; in COPD or chronic bronchitis, RR −0.404; 95% CI −0.864–0.057; in tuberculosis, RR −0.502; 95% CI −0.890 – −0.114). ConclusionsThe results of the present meta-analysis suggest that PBML is effective in both in children and in adults in preventing respiratory tract infections. Our current meta-analysis shows that there is a trend with PBML toward clinically significant results in patients with COPD but it did not quite achieve statistical significance due to the small number of COPD studies.

A Case of Tracheobronchopathia Osteochondroplastica

Received November 29, 2010 Revised December 30, 2010 Accepted January 4, 2011 Address for correspondence Joon Kyoo Lee, MD, PhD Department of OtolaryngologyHead and Neck Surgery, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Hwasun 519-763, Korea Tel +82-61-379-7760 Fax +82-61-379-7761 E-mail joonkyoo@chonnam.ac.kr Tracheobronchopathia Osteochondroplastica (TO) is a rare disease of the trachea characterized by the development of submucosal cartilaginous and bony nodules. The nodules are usually located at the anterior and lateral walls and sometims on the posterior membranous wall. Clinically, the manifestations of TO vary from the incidentally detected asymptomatic to life threatening diseases with airway obstruction. Bronchoscopy is a useful diagnostic tool and radiographic studies also play an important role in the diagnosis of TO. The treatment of TO is reserved for the symptomatic lesion with severe airway narrowing and the prevention of recurrent respiratory infections. Korean J Otorhinolaryngol-Head Neck Surg 2011;54:408-10 Key WordsZZTracheobronchopathia osteoplastica ᆞAirway obstruction.

Tracheobronchopathia Osteochondroplastica: A Rare Large Airway Disorder

Tracheobronchopathia osteochondroplastica (TO) is a rare disorder of the large airways characterized by the development of submucosal cartilaginous and bony nodules. The nodules involve the anterior and lateral walls and typically spare the posterior membranous wall. The clinical presentation of TO is variable and ranges from incidental diagnosis in asymptomatic patients during workup or management for unrelated medical problems, to devastating disease with central airway obstruction. Bronchoscopy remains the gold standard for diagnosing this condition. Radiographic studies play an important role in suggesting the diagnosis of TO and in the follow-up of this condition. The treatment of TO is usually symptomatic. with emphasis on the management and prevention of recurrent respiratory infections. Bronchoscopic or surgical treatment is usually reserved for symptomatic patients with severe airway narrowing and airflow obstruction.

Efficacy ofBacillus clausiispores in the prevention of recurrent respiratory infections in children: a pilot study

Probiotic milk has been previously demonstrated to reduce the number of respiratory infections (RI) among children attending day care centres. Thus, this pilot study was aimed to assess the efficacy and the safety of 3 month treatment with Bacillus clausii in the prevention of recurrent respiratory infections (RRI) in children. Eighty children with RRI were studied: 40 of them were randomly treated with B. clausii for 3 months, and followed up for further 3 months; 40 were included in the control group during the same period. Children treated with B. clausii had shorter duration of RI in comparison with the control group both during the treatment phase (mean 11.7 days vs 14.37; p=0.037) and the follow-up period (mean 6.6 days vs 10.92; p=0.049). This effect was evident also in allergic children during the follow-up. In conclusion, this pilot study provides the first preliminary evidence that B. clausii may exert a significant and persistent impact on RI in children and is safe and well tolerated.

Role of Ribomunyl?? in the Prevention of Recurrent Respiratory Tract Infections in Adults

Recurrent respiratory tract infections (RRTIs) in adults are the result of an imbalance between lung defense mechanisms, and bacterial burden. Antibacterial treatments can temporarily restore the equilibrium between host and bacterial load, but do not prevent recurrence of infection. An alternative approach to prevent recurrence of infection is treatment with an immunostimulant, which provides immune protection against repeated bacterial and viral infection. All immunostimulant products are bacterial in origin: lysates (first generation immunostimulants), or bacterial extracts, like bacterial ribosomes, or membrane proteoglycans. This review highlights the current state of knowledge regarding the use of immunostimulants in adults with RRTIs, taking the ribosomal immunostimulant Ribomunyl((R)) as an example. Many studies are available on the mechanism of action and clinical efficacy in prevention of RRTIs in adults treated with Ribomunyl((R)). The effect of this immunostimulant on anti-infectious responses is explained by a stimulation of both nonspecific (innate) and specific (adaptive) immunity. In order to obtain a global overview of the therapeutic efficacy of Ribomunyl((R)) the most pertinent trials were selected from the literature based on adequate patient numbers and good methodology. Results of double-blind placebo-controlled trials using Ribomunyl((R)) for the treatment of different upper or lower RRTIs have demonstrated a statistically significant reduction in the number of infectious episodes and as a consequence, a decrease in antibacterial consumption, after 3 and 6 months of treatment. The tolerance profile of Ribomunyl((R)) was good in all studies. Economic evaluations suggest that savings can be made in healthcare expenditure, in patients with recurrent episodes of infection. It is concluded that Ribomunyl((R)) is effective in preventing and reducing upper and lower respiratory tract infections in adults. The product may also have an impact on reducing the development of bacterial resistance, as a result of fewer courses of antibacterials required to treat patients with RRTIs.