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Background: Respiratory syncytial virus (RSV) is among the leading causes of hospitalization due to lower respiratory tract infections (LRTIs) in children younger than 5 years worldwide and the second cause of infant death after malaria. RSV infection occurs in almost all the infants before the second year of life with variable clinical severity, often requiring medical assistance. This analysis investigated patients aged 0-5 years with RSV infection focusing on epidemiology, clinical features, and economic burden of RSV-associated hospitalizations in a setting of Italian real clinical practice., Methods: An observational retrospective analysis was conducted on administrative databases of healthcare entities covering around 2.6 million residents of whom 120,000 health-assisted infants aged < 5 years. From 2010 to 2018, pediatric patients were included in the presence of hospitalization discharge diagnosis for RSV infections, and RSV-related acute bronchiolitis or pneumonia. Epidemiology, demographics, clinical picture and costs were evaluated in RSV-infected patients, overall and stratified by age ranges (0-1, 1-2, 2-5 years) and compared with an age-matched general population., Results: Overall 1378 RSV-infected children aged 0-5 years were included. Among them, the annual incidence rate of RSV-related hospitalizations was 175-195/100,000 people, with a peak in neonates aged < 1 year (689-806/100,000). While nearly 85% of infected infants were healthy, the remaining 15% presented previous hospitalization for known RSV risk factors, like preterm birth, or congenital heart, lung, and immune diseases. The economic analysis revealed that direct healthcare costs per patient/year were markedly higher in RSV patients than in the general population (3605€ vs 344€)., Conclusions: These findings derived from the real clinical practice in Italy confirmed that RSV has an important epidemiological, clinical, and economic burden among children aged 0-5 years. While the complex management of at-risk infants was confirmed, our data also highlighted the significant impact of RSV infection in infants born at term or otherwise healthy, demonstrating that all infants need protection against RSV disease, reducing then the risk of medium and long-term complications, such as wheezing and asthma., (© 2024. The Author(s).)

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis., (© 2023. The Author(s).)

Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations., (© 2021. The Author(s).)

Background: Improved neonatal care has resulted in increased survival rates among infants born after only 22 gestational weeks, but extremely preterm children still have an increased risk of neurodevelopmental delays, learning disabilities and reduced cognitive capacity, particularly executive function deficits. Parent-child interaction and parental mental health are associated with infant development, regardless of preterm birth. There is a need for further early interventions directed towards extremely preterm (EPT) children as well as their parents. The purpose of this paper is to describe the Stockholm Preterm Interaction-Based Intervention (SPIBI), the arrangements of the SPIBI trial and the chosen outcome measurements., Methods: The SPIBI is a randomized clinical trial that includes EPT infants and their parents upon discharge from four neonatal units in Stockholm, Sweden. Inclusion criteria are EPT infants soon to be discharged from a neonatal intensive care unit (NICU), with parents speaking Swedish or English. Both groups receive three initial visits at the neonatal unit before discharge during the recruitment process, with a strengths-based and development-supportive approach. The intervention group receives ten home visits and two telephone calls during the first year from a trained interventionist from a multi-professional team. The SPIBI intervention is a strengths-based early intervention programme focusing on parental sensitivity to infant cues, enhancing positive parent-child interaction, improving self-regulating skills and supporting the infant's next small developmental step through a scaffolding process and parent-infant co-regulation. The control group receives standard follow-up and care plus extended assessment. The outcomes of interest are parent-child interaction, child development, parental mental health and preschool teacher evaluation of child participation, with assessments at 3, 12, 24 and 36 months corrected age (CA). The primary outcome is emotional availability at 12 months CA., Discussion: If the SPIBI shows positive results, it could be considered for clinical implementation for child-support, ethical and health-economic purposes. Regardless of the outcome, the trial will provide valuable information about extremely preterm children and their parents during infancy and toddlerhood after regional hospital care in Sweden., Trial Registration: The study was registered in ClinicalTrials.gov in October 2018 (NCT03714633).

Background: Healthcare research funders may undertake various roles to facilitate implementation of research findings. Their ability to enact such roles depends on several factors, knowledge of implementation being one essential requirement. However, previous studies do not assess the type or level of knowledge about implementation that research funders possess. This paper therefore presents findings from a qualitative, inductive study of the implementation knowledge of research funders. Three aspects of this knowledge are explored, namely how research funders define implementation, their level of self-assessed implementation knowledge and the factors influencing their self-assessment of implementation knowledge., Methods: Research funders (n = 18) were purposefully selected from a sample of research funding organisations in Sweden (n = 10). In-depth semi-structured interviews were conducted, recorded and transcribed verbatim. An inductive method using a systematic coding procedure was employed to derive the findings., Results: The research funders defined implementation as either an outcome or a process, with the majority believing that implementation of healthcare research results demands a process, although its complexity varied in the research funders' view. They perceived their own level of implementation knowledge as either limited or substantial, with a majority regarding it as limited. Clinical research experience, clinical experience and task relevance were singled out as the clearest factors affecting the self-assessment of their own implementation knowledge., Conclusions: This study, the first to focus on implementation knowledge of research funders, demonstrates that they are a category of policy-makers who may possess knowledge, based on their previous professional experience, that is comparable to some important findings from implementation research. Consequently, the findings not only pinpoint the relevance of professional experience, but also reveal a lack of awareness and knowledge of the results of implementation research among research funders in charge of healthcare research.

Respiratory diseases account for about 25% of all pediatric consultations, and 10% of these are for asthma. The other main pediatric respiratory diseases, in terms of incidence, are bronchiolitis, acute bronchitis and respiratory infections. Oral corticosteroids, in particular prednisolone, are often used to treat acute respiratory diseases given their anti-inflammatory effects. However, the efficacy of treatment with oral corticosteroids differs among the various types of pediatric respiratory diseases. Notably, also the adverse effects of corticosteroid treatment can differ depending on dosage, duration of treatment and type of corticosteroid administered - a case in point being growth retardation in long-course treatment. A large body of data has accumulated on this topic. In this article, we have reviewed the data and guidelines related to the role of oral corticosteroids in the treatment and management of pediatric bronchiolitis, wheezing, asthma and croup in the attempt to provide guidance for physicians. Also included is a section on the management of acute respiratory failure in children.

Background: We aimed to examine current bedside analgesia/sedation (A/S) and pain assessment (PA) practices in Italian neonatal intensive care units (NICUs) in relation to the findings of an epidemiological European study and recently-introduced national guidelines., Methods: We analyzed the Italian data from the EUROPAIN (EUROpean-Pain-Audit-In-Neonates) prospective observational study on A/S practices that involved 6680 newborns admitted to tertiary-level NICUs in 18 European countries. Demographics, type of assisted ventilation, type and mode of A/S administration and PA were analyzed. Multivariate linear regression models were used to identify factors predicting A/S and PA practices., Results: From October 1 st , 2012 to June 30 th , 2013, thirty Italian NICUs gathered data on 422 newborn: 131 on invasive ventilation (IV); 150 on noninvasive ventilation (NIV); and 141 on spontaneous ventilation (SV). A/S was documented for 35.3% of all infants admitted (86.3% IV; 17.3% NIV; 7.1% SV [p = 0.0001]), and varied considerably between NICUs (as reported in other European countries). Strong analgesics were used in 32.5% of cases, sedatives in 10.2%, mild analgesics in 3.8%. Fentanyl was used in 78.6% of cases, morphine in 8.4%, neuromuscular blockers in 5.3%, midazolam in 22.1%. The performance of PA was documented in 67.5% of all newborn (85.5% IV; 67.3% NIV; 51.1% SV [p = 0.001]). Illness severity, type of ventilation, bedside PA, and number of NICU beds were all factors associated with A/S use on multivariate analysis, while gestational age ≤ 32 weeks, and type of ventilation and presence of a pain team were associated with PA., Conclusions: We documented a generally widespread, but still highly variable use of A/S and PA at Italian NICUs, despite the diffusion of national guidelines. There is an urgent need to improve routine PA to enable customized pain and stress control (and prevention) in all infants., Trial Registration: Clinical Trials.gov # NCT01694745 .

Background: Childhood interstitial lung disease (chILD) is a heterogeneous group of rare disorders characterized by abnormal imaging findings, impaired gas exchange; and is associated with substantial morbidity and mortality. Neuroendocrine cell hyperplasia (NEHI) is a unique sub-group, which is more prevalent in infants and children younger than 2 years of age, and typically manifests with chronic tachypnea, retractions, hypoxemia and failure to thrive. NEHI insidiously appears in the first year of life, subtly masquerading as one of the more common lung diseases of childhood. Therefore, the diagnosis of NEHI is challenging and requires a systematic approach., Case Presentation: We report a case of an infant, with a history of recurrent respiratory infections and wheezing, who presented with persistent hypoxemia (PaO2 88 mmHg) and chronic respiratory symptoms, that prompted an extensive diagnostic work up for chILD; eventually a diagnosis of NEHI was made., Conclusion: NEHI is a rare chILD disorder presenting in the first 2 years of life with common but challenging key clinical features. Increased awareness among pediatricians and prompt recognition of the clinical presentation may enable timely diagnosis and improve disease management and prognosis.

Background: Very few studies have explored the distinguishing features of severe asthma in childhood in Europe, and only one study was conducted in Southern Europe. The aim of this study was to provide a detailed characterization of children with severe asthma treated in specialized pediatric asthma centers across Italy., Methods: We conducted a web-based data collection of family, environmental, clinical and laboratory characteristics of 41 patients aged 6-17 years with severe asthma, defined according to the recent guidelines of the European Respiratory Society and the American Thoracic Society, and 78 age-matched peers with non-severe persistent asthma. The patients have been enrolled from 16 hospital-based pediatric pulmonology and allergy centers in Northern, Central, and Southern Italy. Logistic regression analysis assessed the relationship between patients' characteristics and severe asthma or non-severe persistent asthma., Results: Features independently and significantly associated with severe asthma included lifetime sensitization to food allergens [Odds ratio (OR), 4.73; 95 % Confidence Interval (CI), 1.21-18.53; p = 0.03], lifetime hospitalization for asthma (OR, 3.71; 95 % CI, 1.11-12.33; p = 0.03), emergency-department visits for asthma during the past year (OR = 11.98; 95 % CI, 2.70-53.11; p = 0.001), and symptoms triggered by physical activity (OR = 12.78; 95 % CI, 2.66-61.40; p = 0.001). Quality-of-life score was worse in patients with severe asthma than in subjects with non-severe persistent asthma (5.9 versus 6.6, p = 0.005). Self-perception of wellbeing was compromised in more than 40 % of patients in both groups. Children with severe asthma had lower spirometric z scores than non-severe asthmatic peers (all p < 0.001), although 56 % of them had a normal forced expiratory volume in 1 s. No differences were found between the two groups for parental education, home environment, patients' comorbidities, adherence to therapy, exhaled nitric oxide values, and serum eosinophils and IgE ., Conclusions: As expected, children with severe asthma had more severe clinical course and worse lung function than peers with non-severe persistent asthma. Unlike previous reports, we found greater sensitization to food allergens and similar environmental and personal characteristics in patients with severe asthma compared to those with non-severe persistent asthma. Psychological aspects are compromised in a large number of cases and deserve further investigation.

Background: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13)., Methods: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9%), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction., Results: S. pneumoniae was identified in the swabs of 192 subjects (45.4%): 48.4% of whom were aged <10 years, 46.9% aged 10-14 years, and 4.7% aged ≥15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95% confidence interval [95% CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95% CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95% CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95% CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects., Conclusions: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

Background: Implementation of clinical research results is challenging, yet the responsibility for implementation is seldom addressed. The process from research to the use of clinical research results in health care can be facilitated by research funders. In this paper, we report the roles of ten Swedish research funders in relation to implementation and their views on responsibilities in implementation., Findings: Ten cases were studied and compared using semi-structured interviews. In addition, websites and key documents were reviewed. Eight facilitative roles for research funders in relation to the implementation of clinical research results were identified. Three of them were common for several funders: "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge." Moreover, the research funders identified six different actors responsible for implementation, five of which belonged to the healthcare setting. Collective and organizational responsibilities were the most common forms of responsibilities among the identified actors responsible for implementation., Conclusions: The roles commonly identified by the Swedish funders, "Advocacy work," "Monitoring implementation outcomes," and "Dissemination of knowledge," seem feasible facilitative roles in relation to the implementation of clinical research results. However, many actors identified as responsible for implementation together with the fact that collective and organizational responsibilities were the most common forms of responsibilities entail a risk of implementation becoming no one's responsibility.

Background: The Paediatric Residency Program (PRP) of Padua, Italy, developed a set of questionnaires to assess the quality of the training provided by each faculty member, the quality of the professional experience the residents experienced during the various rotations and the functioning of the Resident Affair Committee (RAC), named respectively: "Tutor Assessment Questionnaire" (TAQ), "Rotation Assessment Questionnaire" (RAQ), and RAC Assessment Questionnaire". The process that brought to their validation are herein presented., Method: Between July 2012 and July 2013, 51 residents evaluated 26 tutors through the TAQ, and 25 rotations through the RAQ. Forty-eight residents filled the RAC Assessment Questionnaire. The three questionnaires were validated through a many-facet Rasch measurement analysis., Results: In their final form, the questionnaires produced measures that were valid, reliable, unidimensional, and free from gender biases. TAQ and RAQ distinguished tutors and rotations into 5-6 levels of different quality and effectiveness. The three questionnaires allowed the identification of strengths and weaknesses of tutors, rotations, and RAC. The agreement observed among judges was coherent to the predicted values, suggesting that no particular training is required for developing a shared interpretation of the items., Conclusions: The work herein presented serves to enrich the armamentarium of tools that resident medical programs can use to monitor their functioning. A larger application of these tools will serve to consolidate and refine further the results presented.

Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization in children less than 1 year of age worldwide. It is usually a mild disease, but some children may develop severe symptoms, requiring hospital admission and ventilatory support in the ICU. Infants with pre-existing risk factors (prematurity, bronchopulmonary dysplasia, congenital heart diseases and immunodeficiency) may be predisposed to a severe form of the disease. Clinical diagnosis of bronchiolitis is manly based on medical history and physical examination (rhinorrhea, cough, crackles, wheezing and signs of respiratory distress). Etiological diagnosis, with antigen or genome detection to identify viruses involved, may have a role in reducing hospital transmission of the infection. Criteria for hospitalization include low oxygen saturation (<90-92%), moderate-to-severe respiratory distress, dehydration and presence of apnea. Children with pre-existing risk factors should be carefully assessed.To date, there is no specific treatment for viral bronchiolitis, and the mainstay of therapy is supportive care. This consists of nasal suctioning and nebulized 3% hypertonic saline, assisted feeding and hydration, humidified O2 delivery. The possible role of any pharmacological approach is still debated, and till now there is no evidence to support the use of bronchodilators, corticosteroids, chest physiotherapy, antibiotics or antivirals. Nebulized adrenaline may be sometimes useful in the emergency room. Nebulized adrenaline can be useful in the hospital setting for treatment as needed. Lacking a specific etiological treatment, prophylaxis and prevention, especially in children at high risk of severe infection, have a fundamental role. Environmental preventive measures minimize viral transmission in hospital, in the outpatient setting and at home. Pharmacological prophylaxis with palivizumab for RSV bronchiolitis is indicated in specific categories of children at risk during the epidemic period. Viral bronchiolitis, especially in the case of severe form, may correlate with an increased incidence of recurrent wheezing in pre-schooled children and with asthma at school age.The aim of this document is to provide a multidisciplinary update on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications, identify gaps in knowledge and drive future research.

Background: There are increasing evidence highlighting the importance of incorporating issues of global health into pre- and post-graduate medical curricula. Medical international cooperation is a fundamental component of strategies to include global health issues in post-graduate medical curricula., Methods: Here we describe a seven-year cooperation between the Non Governmental Organization (NGO) "Doctors for Africa CUAMM" and the Pediatric Residency Program (PRP) of the University of Padua (Italy) that offers residents a well-articulated personalized international child's health (ICH) elective in Africa, called "Junior Project Officer". The elective includes: a careful candidate selection process; pre-departure educational course; preceptorship in Padua and Africa, personalized learning objectives, a personalized job description, a six-month hands-on learning experience in Africa, evaluation of the experience, and formal private and open feed-backs/reports., Results: Between 2006 and 2012, 14 residents aged from 27 to 31 years, six attending the III, nine the IV and two the V year of residency completed the six-month stage in Africa. All worked in pediatric in-patient units; seven also worked in out-patient clinics, six in emergency rooms and seven in community health centers. Eleven were involved in teaching activities and four in clinical research projects. All residents claimed to have achieved their learning objectives., Conclusions: A strong partnership between the NGO and the PRP, and well-articulated personalized learning objectives and job description contributed to a successful ICH elective.

Background: In order to help assess resident performance during training, the Residency Affair Committee of the Pediatric Residency Program of the University of Padua (Italy) administered a Resident Assessment Questionnaire (ReAQ), which both residents and faculty were asked to complete. The aim of this article is to present the ReAQ and its validation., Methods: The ReAQ consists of 20 items that assess the six core competencies identified by the Accreditation Council of Graduate Medical Education (ACGME). A many-facet Rasch measurement analysis was used for validating the ReAQ., Results: Between July 2011 and June 2012, 211 evaluations were collected from residents and faculty. Two items were removed because their functioning changed with the gender of respondents. The step calibrations were ordered. The self evaluations (residents rating themselves) positively correlated with the hetero evaluations (faculty rating residents; Spearman's ρ = 0.75, p < 0.001). Unfortunately, the observed agreement among faculty was smaller than expected (Exp = 47.1%; Obs = 41%), which indicates that no enough training to faculty for using the tool was provided., Conclusions: In its final form, the ReAQ provides a valid unidimensional measure of core competences in pediatric residents. It produces reliable measures, distinguishes among groups of residents according to different levels of performance, and provides a resident evaluation that holds an analogous meaning for residents and faculty.

Background: Tuber magnatum, the Italian white truffle, is the most sought-after edible ectomycorrhizal mushroom. Previous studies report the difficulties of detecting its mycorrhizas and the widespread presence of its mycelium in natural production areas, suggesting that the soil mycelium could be a good indicator to evaluate its presence in the soil. In this study a specific real-time PCR assay using TaqMan chemistry was developed to detect and quantify T. magnatum in soil. This technique was then applied to four natural T. magnatum truffières located in different regions of Italy to validate the method under different environmental conditions., Results: The primer/probe sets for the detection and quantification of T. magnatum were selected from the ITS rDNA regions. Their specificity was tested in silico and using qualitative PCR on DNA extracted from 25 different fungal species. The T. magnatum DNA concentration was different in the four experimental truffières and higher in the productive plots. T. magnatum mycelium was however also detected in most of the non-productive plots. Ascoma production during the three years of the study was correlated with the concentration of T. magnatum DNA., Conclusions: Taken together, these results suggest that the specific real-time PCR assay perfected in this study could be an useful tool to evaluate the presence and dynamics of this precious truffle in natural and cultivated truffières.

Background: Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations., Methods: To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode., Results: The percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma., Conclusions: A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.