[The effectiveness of BIFIFORM KIDS in the prevention of the incidence of acute respiratory infections in children].

Probiotics are widely used as a means of dietary correction of the intestinal microbiota in patients not only with alimentary, but also with allergic and inflammatory diseases. They have systemic effects on the human organism. However, the diversity of the composition of probiotic complexes complicates the determination of the beneficial effects of specific microorganisms on the human body. These circumstances call for more research. Investigation of the effect of probiotic intake on the levels of various cytokines may explain the mechanisms of the beneficial effect of probiotic intake on the functioning of the immune system. Objective - to study the effectiveness of the probiotic Bifiform Kids for the prevention of respiratory infections in children with recurrent respiratory infections with gastrointestinal allergy symptoms. Material and methods. The prospective randomized controlled trial included 92 children aged from 4 to 5 years who suffers from more than 5 episodes of respiratory infections per year with gastrointestinal allergy symptoms. Patients from the main group (n=46) were prescribed 2 chewable tablets Bifiform Kids (Lactobacillus rhamnosus GG not less than 1×109 CFU, Bifidobacterium animalis spp. lactis not less than 1×109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg in each) twice per day within 21 days. Patients from the control group (n=46) were prescribed no probiotics during the study period. The study included the measurement of blood serum levels of immunoglobulins A, M, G (by immunoturbodimetry) and E, as well as the concentration of cytokines IL-17, IL-10 (by enzyme immunoassay). Measurements were performed at the 1st day of the study, at the 21st day of the study, and 6 months after the study initiation. The microbiota composition was determined by sequencing the bacterial 16S rRNA genes in DNA preparations isolated from stool samples collected at the start of the study and after 21 days. The Shannon index was calculated for the species of detected bacteria to determine the diversity of the microbiome. The effectiveness of disease prevention was measured by calculating the prevention index and the efficiency coefficient based on the incidence of respiratory infections in both groups during the observation period (6 months). Results. In the main group, the volume of the commensal flora decreased 3 weeks after the study initiation: Enterobacter from 18.3±19.3 to 10.5±18.1%; Enterococcus from 8.7±16.1 to 3.1±10.0%; Clostridium from 3.1±8.1 to 0.5±2.2%. There was a statistically significant increase in the proportion of representatives of the genus Bifidobacterium by 2.2 times (from 16.9±26.4 to 36.5±31.5%, p=0.0017) and a decrease in the Shannon index from 1.1±2.1 up to 0.4±1.1 (p<0.05). In the control group, there were no statistically significant changes in the microbiota content. In the main group, after 21 days, the blood IL-10 level increased from 11.3±15.4 to 15.7±13.4 pg/ml, and the IL-17 concentration decreased from 8.9±7.7 to 6.5±7.1 pg/ml (p=<0.05) while maintaining this trend by the 6th month of observation. There were no changes in these indicators in children from the control group. The main group demonstrated a significant (р=<0.05) decrease in the level of IgE from 184±121 to 104±67 and 114±54 kU/l, and a significant increase in IgA from 0.73±0.45 to 1.33±0.65 and 1.21±0.57 g/l after 3 weeks and at the end of the probiotic intake, respectively. The level of IgA in the main group remained higher during the study compared to the control group. The main group demonstrated a 3-fold decrease in the incidence of respiratory infections in comparison with the control group. The efficiency index was 3.21, the therapeutic response was 69%. Conclusion. The results of the study show the effectiveness of the complex probiotic for the respiratory infections prevention in children with gastrointestinal allergy symptoms.

Recurrent respiratory infections between immunity and atopy.

Recurrent respiratory infections (RRIs) are frequent in children and are characterized by more than 6 airway infections in 1 year or more than 1 upper airway infection per month in the period between September and April or more than 3 lower airway infections in 1 year. Often pediatric RRIs are related to predisposing factors, such as reduced airway size, poor tussive reflex, and immaturity of the immune system. RRIs due to immature immune system are a transient condition, with spontaneous resolution in the school age. However, some RRIs are expression of more complex diseases. Red flags are the onset of symptoms in the first year of life, the involvement of other systems, unusual pathogens, slowing of growth, severe infections of the lower airways, and recurrence of the infection site. To help the pediatrician in the RRI differential diagnosis, we have created a roadmap based on scientific literature data and clinical practice that identifies 6 macro areas: immunodeficiencies, simple minimal genetic immunodeficiency, atopy, obesity, nutritional deficiencies, autoinflammatory diseases, and complex diseases.

Effects of pidotimod and bifidobacteria mixture on clinical symptoms and urinary metabolomic profile of children with recurrent respiratory infections: a randomized placebo-controlled trial.

BACKGROUND: Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators as pidotimod or probiotics, but there is limited evidence of their efficacy on clinical features or on urine metabolic profile. OBJECTIVE: To evaluate whether pidotimod and/or bifidobacteria can reduce RRI morbidity and influence the urine metabolic profile in preschool children. MATERIALS AND METHODS: Children aged 3-6 years with RRI were enrolled in a four-arm, exploratory, prospective, randomized, double-blinded, placebo-controlled trial. Patients were randomly assigned to receive pidotimod plus bifidobacteria, pidotimod plus placebo, bifidobacteria plus placebo or double placebo for the first 10 days of each month over 4 consecutive months. Respiratory symptoms and infections were recorded with a daily diary by parents during the study. Metabolomic analyses on urine samples collected before and after treatment were performed. RESULTS: Compared to placebo, children receiving pidotimod, alone or with bifidobacteria, had more symptom-free days (69 versus 44, p = 0.003; and 65 versus 44, p = 0.02, respectively) and a lower percentage of days with common cold (17% versus 37%, p = 0.005; and 15% versus 37%, p = 0.004, respectively). The metabolomic analysis showed that children treated with Pidotimod (alone or in combination with bifidobacteria) present, respect to children treated with placebo, a biochemical profile characterized by compounds related to the pathway of steroids hormones, hippuric acid and tryptophan. No significant difference in the metabolic profile was found between children receiving bifidobacteria alone and controls. CONCLUSIONS: Preschool children with RRI treated with pidotimod have better clinical outcomes and a different urine metabolomic profile than subjects receiving placebo. Further investigations are needed to clarify the connection between pidotimod and gut microbiome.

Follow-up and outcome of symptomatic partial or absolute IgA deficiency in children.

Selective IgA deficiency is defined as absolute or partial when serum IgA level is < 7 mg/dl or 2 SD below normal for age, respectively. Few data are available on partial selective IgA deficiency, as probably most children with low serum IgA are seldom referred to a specialist clinic in common pediatric practice. The aim of our study was to better define the profile of both symptomatic forms and their clinical outcome in a pediatric immunology setting. Thus, clinical and immunological data from 103 symptomatic patients with selective IgA deficiency (53 absolute and 50 partial), 4-18 years of age, were collected at diagnosis and 80 patients (44 absolute and 36 partial) were monitored for a mean period of 5 years. Also, the prevalence of TNFRSF13B mutations has been assessed in 56 patients. The most common clinical features were infections (86/103; 83%), allergy (39/103; 38%), and autoimmunity (13/103; 13%). No significative differences were observed between absolute and partial selective IgA deficiency patients. However, a significative difference in the rate of IgA normalization between partial and absolute selective IgA deficiency patients (33 vs 9%, p = 0.01) was detected. Furthermore, a lower incidence of infections was associated to a normalization reversal compared to a final absolute or partial defect status (12 vs 53 and 64% respectively, p < 0.01).Conclusions: Regardless of a diagnosis of absolute or partial defect, monitoring of symptomatic patients with selective IgA deficiency is recommended overtime for prompt identification and treatment of associated diseases. Further, diagnostic workup protocols should be revisited in children with IgA deficiency. What is Known: ● Selective IgA Deficiency is the most common primary immunodeficiency and is usually asymptomatic. ● Symptomatic pediatric patients with selective IgA deficiency mostly suffer with respiratory and gastrointestinal infections. What is New: ● Symptomatic children with partial IgA defect may have similar clinical, immunological, and genetic features than symptomatic children with absolute IgA deficiency. ● Symptomatic children with partial IgA deficiency deserve accurate monitoring for associated diseases as per children with absolute IgA deficiency.

Metabolomic profile of children with recurrent respiratory infections.

Recurrent respiratory infections (RRI) represent a widespread condition which has a severe social and economic impact. Immunostimulants are used for their prevention. It is crucial to better characterize children with RRI to refine their diagnosis and identify effective personalized prevention strategies. Metabolomics is a high-dimensional biological method that can be used for hypothesis-free biomarker profiling, examining a large number of metabolites in a given sample using spectroscopic techniques. Multivariate statistical data analysis then enables us to infer which metabolic information is relevant to the biological characterization of a given physiological or pathological condition. This can lead to the emergence of new, sometimes unexpected metabolites, and hitherto unknown metabolic pathways, enabling the formulation of new pathogenetic hypotheses, and the identification of new therapeutic targets. The aim of our pilot study was to apply mass-spectrometry-based metabolomics to the analysis of urine samples from children with RRI, comparing these children's biochemical metabolic profiles with those of healthy peers. We also compared the RRI children's and healthy controls' metabolomic urinary profiles after the former had received pidotimod treatment for 3 months to see whether this immunostimulant was associated with biochemical changes in the RRI children's metabolic profile. 13 children (age range 3-6 yeas) with RRI and 15 matched per age healthy peers with no history of respiratory diseases or allergies were enrolled. Their metabolomic urine samples were compared before and after the RRI children had been treated with pidotimod for a period of 3 months. Metabolomic analyses on the urine samples were done using mass spectrometry combined with ultra-performance liquid chromatography (UPLC-MS). The resulting spectroscopic data then underwent multivariate statistical analysis and the most relevant variables characterizing the two groups were identified. Data modeling with post-transformation of PLS2-Discriminant Analysis (ptPLS2-DA) generated a robust model capable of discriminating the urine samples from children with RRI from those of healthy controls (R2=0.92,Q2CV7-fold=0.75, p-value<0.001). The dataset included 1502 time per mass variables, and 138 of them characterized the difference between the two groups. Thirty-five of these distinctive 138 variables persisted in the profiles of the children with RRI after pidotimod treatment. Metabolomics can discriminate children with RRI from healthy controls, suggesting that the former have a dysregulated metabolic profile. Among the variables characterizing children with RRI there are metabolites that may reflect the presence of a different microbiome. After pidotimod treatment, the metabolic profile of the children with RRI was no longer very different from that of the healthy controls, except for the persistence of some microbiome-related variables. We surmise that pidotimod partially "restores" the altered metabolic profile of children with RRI, without modifying the metabolites related to the composition of the gut microbiota. In the light of these results, we hypothesize a potential synergic effect of the combined use of immunostimulants and probiotics for the purpose of prevention in children with RRI.

Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children.

BACKGROUND: To analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. METHODS: The study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3µg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x(2) test. RESULTS: All of the children showed antipneumococcal antibody levels >1.3µg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. CONCLUSION: The asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.

Food allergy is associated with recurrent respiratory tract infections during childhood.

INTRODUCTION: To find out whether children with food allergy have an increased risk of recurrent upper and lower respiratory tract infections and of asthma. AIM: To describe the clinical profile of children diagnosed with food allergy referred to the Allergy Clinic. MATERIAL AND METHODS: We conducted a retrospective study to assess the patients' demographic, anthropometric and clinical data. The analysis included data of all children by the age of 10 years (registered with the Allergy Clinic between 2012 and 2013) in whom IgE mediated food allergy had been diagnosed during 18 months of observation. RESULTS: We included 280 children into the analysis. Recurrent respiratory tract infections (rRTI), asthma and gastrointestinal (GI) symptoms were observed in 153 (54.6%), 96 (34.3%), 39 (13.9%), respectively, with a significant increasing trend across age-subgroups. In children from 1 to 2 years old, sensitization to ß-lactoglobulin increased the risk of rRTI (OR = 3.91; 95% CI: 1.03-14.87). In older children sensitization to allergens other than milk or egg decreases the risk of rRTI (OR = 0.25; 95% CI: 0.10-0.62); sensitization to egg decreased the risk of asthma diagnosis (OR = 0.09; 95% CI: 0.01-0.75). We did not identify food allergens which change the risk of GI symptoms in children. This finding was consistent throughout all age-subgroups. CONCLUSIONS: Sensitization to ß-lactoglobulin increased the risk of rRTI in children under 2 years of age nearly four times. The presence of sensitization to food allergens above 3 years of age did not increase the risk of developing clinical presentation of food allergy other than atopic dermatitis.

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.

A case report of unusual recurrent bronchopneumonia infections in Mounier-Kuhn syndrome.

Mounier-Kuhn syndrome is a rare airway disease characterized by tracheal and bronchial dilatation, primarily affecting middle-aged men. We present a case of Mounier-Kuhn syndrome in a 40-year-old man with a history of recurrent respiratory infections since adolescence. The diagnostic journey involved a multidisciplinary approach incorporating clinical evaluation, radiological imaging, and bronchoscopy. Computed tomography findings, including maximum intensity projection reconstructions and 3D rendering, facilitated the diagnosis by revealing significant airway dilation and associated abnormalities. Treatment primarily focused on supportive measures, including antibiotic therapy and respiratory physiotherapy. This case underscores the importance of considering Mounier-Kuhn syndrome in patients with recurrent respiratory infections and highlights the role of advanced imaging techniques in diagnosis.

[Characterization of otorhinolaryngologic manifestations in children with mucopolysaccharide storage disease typeâ and type â ¡].

Objective:To analyze the characteristics of otorhinolaryngological clinical manifestations in children with Mucopolysaccharide（MPS） type Ⅰ and type II in order to improve the knowledge of otorhinolaryngologists about this disease. Methods:Clinical data related to 55 children with MPS type Ⅰ and type II were retrospectively analyzed to investigate the clinical manifestations of MPS in ENT. Results:All 40 patients（72.72%） with MPS had at least one ENT symptom during the course of the disease, with 95% of them having an ENT symptom prior to the diagnosis of MPS; upper airway obstruction was the most common ENT symptom（34, 85.00%）, followed by recurrent upper respiratory tract infections（23, 57.50%）, and lastly, hearing loss（11, 27.50%）; all 26 patients had undergone at least one surgical procedure, of which 15（57.69%） had undergone ENT surgery, and all of these patients underwent ENT surgery before diagnosis. The most common ENT surgery was adenoidectomy. Conclusion:Early clinical manifestations of MPS patients are atypical, but the early and prevalent appearance of otolaryngologic symptoms and increased awareness of the disease among otolaryngologists has a positive impact on the prognosis of MPS.

Recurrent Respiratory Infections in Children with Down Syndrome: A Review.

Down Syndrome (DS) is the most common chromosomal abnormality compatible with life. The life of patients suffering from DS can be strongly impacted by Recurrent Respiratory tract Infections (RRIs), leading to an increased rate of hospitalisation, a higher need for intensive care and fatality. With a literature review, we summarise here the main etiological factors for RRI in this category of patients, particularly focusing on airway malformations such as tracheomalacia, tracheal bronchus and bronchomalacia, comorbidities associated with the syndrome, like congenital heart diseases, dysphagia, gastroesophageal reflux, musculoskeletal involvement and obesity, and immunologic impairments, involving both innate and adaptive immunity. For these patients, a multidisciplinary approach is imperative as well as some preventive strategies, in particular vaccinations in accordance with their national schedule for immunization.

Why do some Children Get Sick with Recurrent Respiratory Infections?

Respiratory tract infections (RTI) represent a frequent condition, particularly among preschool children, with an important burden on the affected children and their families. It has been estimated that recurrent RTIs affect up to 25% of children during the first 4 years of life. These infections are mainly caused by viruses and are generally self-limiting. Social and environmental factors have been studied in determining the incidence of recurrent RTIs and the mostly recognized are precocious day care attendance, tobacco exposure and pollution. Primary immune defects, local anatomical factors, and genetic disorders such as primary ciliary dyskinesia or cystic fibrosis, may be also involved in recurrent RTIs of a subgroup of children, typically characterized by more severe and chronic symptoms. However, there is increasing awareness that RTIs have a complex pathophysiology and that some underrecognized factors, including genetic susceptibility to infections, low levels of some micronutrients, and respiratory microbiota might shape the probability for the child to develop RTIs. The sum (i.e. the number) of these factors may help in explaining why some children get sick for RTIs whilst other not. In some children iatrogenic factors, including improper use of antibiotics and NSAIDS or glucocorticoids might also aggravate this condition, further weakening the host's immune response and the possibly of establishing a "vicious circle". The present review aims to focus on several possible factors involved in influencing RTIs and to propose a unifying hypothesis on pathophysiological mechanisms of unexplained recurrent RTIs in children.

Chronic respiratory disorders due to aberrant innominate artery: a case series and critical review of the literature.

BACKGROUND: Tracheal compression (TC) due to vascular anomalies is an uncommon, but potentially serious cause of chronic respiratory disease in childhood. Vascular slings are congenital malformations resulting from abnormal development of the great vessels; in this group of disorders the most prevalent entity is the aberrant innominate artery (AIA). Here we provide a report on diagnosis and treatment of AIA in nine children with unexplained chronic respiratory symptoms. We describe the cases, perform a literature review, and provide a discussion on the diagnostic workup and treatment that can help manage AIA. METHODS: Clinical history, diagnostic procedures and treatment before and after the AIA diagnosis were retrospectively reviewed in nine children (5 boys and 4 girls), who were referred for recurrent-to-chronic respiratory manifestations over 10 years (2012-2022). We performed a comprehensive report on the ongoing clinical course and treatment as well as an electronic literature search on the topic. RESULTS: Diagnoses at referral, before AIA was identified, were chronic dry barking cough associated with recurrent pneumonia (n = 8, 89%), lobar/segmental atelectasis (n = 3, 33%), atopic/non atopic asthma (n = 3, 33%); pneumomediastinum with subcutaneous emphysema complicated the clinical course in one case. When referred to our Unit, all patients had been previously treated with repeated antibiotic courses (n = 9, 100%), alone (n = 6, 67%) or combined with prolonged antiasthma medications (n = 3, 33%) and/or daily chest physiotherapy (n = 2, 22%), but reported only partial clinical benefit. Median ages at symptom onset and at AIA diagnosis were 1.5 [0.08-13] and 6 [4-14] years, respectively, with a relevant delay in the definitive diagnosis (4.5 years). Tracheal stenosis at computed tomography (CT) was ≥ 51% in 4/9 cases and ≤ 50% in the remaining 5 subjects. Airway endoscopy was performed in 4 cases with CT evidence of tracheal stenosis ≥ 51% and confirmed CT findings. In these 4 cases, the decision of surgery was made based on endoscopy and CT findings combined with persistence of clinical symptoms despite medical treatment. The remaining 5 children were managed conservatively. CONCLUSIONS: TC caused by AIA may be responsible for unexplained chronic respiratory disease in childhood. Early diagnosis of AIA can decrease the use of expensive investigations or unsuccessful treatments, reduce disease morbidity, and accelerate the path toward a proper treatment.

Association of recurrent upper respiratory tract infections with low production of oxygen intermediates in children.

OBJECTIVES: Upper respiratory tract infections in children generally have significant morbidity and mortality. There is little data available about functional immaturity of the immune system and the child's susceptibility to infections at the beginning of their lives, thus, justifying a more specific immunological analysis. METHOD: Analysis of hemograms and innate and adaptive immune responses in 95 children between age 1 to 6 years with episodes of recurrent respiratory infections (test group n = 39) and without these episodes (control group n = 56) was carried out. The production of reactive oxygen intermediates by peripheral blood cells stimulated by phorbol myristate acetate was analyzed. Additionally, the number of B lymphocytes, auxiliary T lymphocytes, and cytotoxic cells was determined using flow cytometry. RESULTS: Results from both groups did not show statistically significant differences in red blood cells, total leukocytes count, and the differential neutrophils, eosinophils, basophils, lymphocytes, and monocytes count. The analysis of the number of B lymphocytes, auxiliary T lymphocytes (LTCD4), and cytotoxic cells (LTCD8) also did not show any difference between both groups. However, the production of radical oxygen intermediates was significantly reduced in the test group as compared to the control group (p < 0.05). CONCLUSIONS: There was no difference in the analysis of hemograms, leukograms, or the number of lymphocytes, LTCD4, LTCD8, or LTCD19. The reduced production of oxygen intermediates in the affected group suggests that these children's microbicide capacity is compromised, which may be related to their recurrent respiratory infections.

Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: A Delphi study.

Recurrent infections of upper and lower respiratory tract have an important clinical and economic impact, which can be reduced through appropriate preventive measures, including the use of immunomodulating agents, such as OM-85, which proved to be effective and safe in both adults and children. Although OM-85 can be useful for the prevention of respiratory tract infections, it is still underused in clinical practice. In order to evaluate the level of awareness of the disease burden of recurrent respiratory infections in adults and children and to assess the level of agreement on the prophylactic and therapeutic approach to the disease, including the use of immunomodulants, a Delphi study was performed. A board of six experts in the field of respiratory infections was appointed to elaborate a series of statements covering four main topics (disease, prevention, OM-85, and future strategies), which were thereafter voted by a panel of 30 experts. Results showed that prevention is unanimously recognized as the most important intervention to reduce disease burden, and the use of immunomodulation to improve the effectiveness of vaccination is gaining increasing favor among clinicians. In this respect, OM-85 is recognized as the most studied immunomodulating agent currently available, whose efficacy and safety make it a valuable tool to optimize the management of recurrent respiratory infections in both adults and children. In particular, the combined use of OM-85 and influenza vaccine was recognized as an effective and safe approach to improve the current prevention strategies in order to reduce the burden of recurrent respiratory infections.

Tracheobronchomegaly (Mounier-Kuhn Syndrome) with CT and bronchoscopic correlation: A case report.

Tracheobronchomegaly, or Mounier-Kuhn syndrome, is a clinical and radiological entity characterized by marked dilatation of the trachea and bronchi as a result of severe atrophy of the elastic fibers, with thinning of the muscularis, and the formation of diverticula between the cartilaginous rings. The etiopathogenesis is uncertain and may be congenital or acquired. The clinical signs are not specific and are frequently revealed by recurrent respiratory infections and chronic cough. The diagnosis of Mounier-Kuhn syndrome is based on well-documented measurements of the trachea and main bronchi performed on a chest computed tomography scan. The management of patients is based on symptomatic treatment and may require, in severe cases, the use of endoscopic treatment by stent placement or surgical tracheobronchoplasty. We present a case of a 59yearold patient with recurrent respiratory infections that required several hospitalizations. Diagnosed with Mounier Kuhn syndrome, the thoracic computed tomography scan demonstrated a dilated trachea until the bifurcation and focal points of bronchial dilatation. Bronchoscopic examination showed a dilated and deformed trachea with the presence of diverticula on the tracheal anterior wall. The diameter of the trachea was reduced by more than 50% during expiration and coughing. For this reason, Mounier-Kuhn syndrome should be considered in cases of recurrent respiratory infection or persistent respiratory symptoms.

Development of an International Database for a Rare Genetic Disorder: The MECP2 Duplication Database (MDBase).

The natural history of MECP2 duplication syndrome (MDS), a rare X-linked neurodevelopmental disorder with an estimated birth prevalence of 1/150,000 live births, is poorly understood due to a lack of clinical data collected for research. Such information is critical to the understanding of disease progression, therapeutic endpoints and outcome measures for clinical trials, as well as the development of therapies and orphan products. This clinical information can be systematically collected from caregivers through data collation efforts-yet, no such database has existed for MDS before now. Here, in this methodological study, we document the development, launch and management of the international MECP2 Duplication Database (MDBase). The MDBase consists of an extensive family questionnaire that collects information on general medical history, system-specific health problems, medication and hospitalisation records, developmental milestones and function, and quality of life (for individuals with MDS, and their caregivers). Launched in 2020, in its first two years of operation the MDBase has collected clinical data from 154 individuals from 26 countries-the largest sample size to date. The success of this methodology for the establishment and operation of the MDBase may provide insight and aid in the development of databases for other rare neurodevelopmental disorders.

Long-term treatment with nebulized colistin in oncological patients with recurrent respiratory infections.

OBJECTIVES: To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients. METHODS: A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017). RESULTS: Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified. CONCLUSIONS: Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.